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Journal of Zhejiang University SCIENCE B 2014 Vol.15 No.1 P.16-42

http://doi.org/10.1631/jzus.B1300106


Prostate cancer: the need for biomarkers and new therapeutic targets*


Author(s):  Juliana Felgueiras, Joana Vieira Silva, Margarida Fardilha

Affiliation(s):  . Laboratory of Signal Transduction, Centre for Cell Biology, Biology Department and Health Sciences Department, University of Aveiro, 3810-193 Aveiro, Portugal

Corresponding email(s):   mfardilha@ua.pt

Key Words:  Prostate cancer (PCa), Biomarker, Androgen, Estrogen, Cell signaling pathway, Therapeutical target


Juliana Felgueiras, Joana Vieira Silva, Margarida Fardilha. Prostate cancer: the need for biomarkers and new therapeutic targets[J]. Journal of Zhejiang University Science B, 2014, 15(1): 16-42.

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publisher="Zhejiang University Press & Springer",
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T1 - Prostate cancer: the need for biomarkers and new therapeutic targets
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Abstract: 
prostate cancer (PCa) incidence and mortality have decreased in recent years. Nonetheless, it remains one of the most prevalent cancers in men, being a disquieting cause of men’s death worldwide. Changes in many cell signaling pathways have a predominant role in the onset, development, and progression of the disease. These include prominent pathways involved in the growth, apoptosis, and angiogenesis of the normal prostate gland, such as androgen and estrogen signaling, and other growth factor signaling pathways. Understanding the foundations of PCa is leading to the discovery of key molecules that could be used to improve patient management. The ideal scenario would be to have a panel of molecules, preferably detectable in body fluids, that are specific and sensitive biomarkers for PCa. In the early stages, androgen deprivation is the gold standard therapy. However, as the cancer progresses, it eventually becomes independent of androgens, and hormonal therapy fails. For this reason, androgen-independent PCa is still a major therapeutic challenge. By disrupting specific protein interactions or manipulating the expression of some key molecules, it might be possible to regulate tumor growth and metastasis formation, avoiding the systemic side effects of current therapies. Clinical trials are already underway to assess the efficacy of molecules specially designed to target key proteins or protein interactions. In this review, we address that recent progress made towards understanding PCa development and the molecular pathways underlying this pathology. We also discuss relevant molecular markers for the management of PCa and new therapeutic challenges.

前列腺癌:亟待肿瘤标志物和治疗新靶点

研究目的:这篇综述系统地阐述了前列腺癌的发生、发展、相关分子信号通路以及分子标志物用于前列腺癌的临床诊断和前列腺癌诊治所面临的挑战。
重要结论:许多分子信号通路通过影响细胞生长、凋亡、血管生成等病理生理过程而参与了前列腺癌的起始、发生和发展。这些研究基础有助于寻找前列腺癌的肿瘤标志物和改进前列腺癌的治疗。虽然去势治疗是早期前列腺癌治疗的金标准,但是晚期的激素抵抗型前列腺癌(CRPC)的治疗仍面临着巨大的挑战。所幸的是,目前研究发现可以通过切断特异的蛋白-蛋白相互作用或者通过调节某些影响肿瘤生长和转移的关键分子来治疗前列腺癌,能减少传统治疗所带来的副作用;相关临床研究已开始实施。这些研究进展给前列腺癌的诊治带来了新的曙光。

关键词:前列腺癌;肿瘤标志物;分子信号通路;治疗新靶点

Darkslateblue:Affiliate; Royal Blue:Author; Turquoise:Article

References

[1] Aaronson, D.S., Muller, M., Neves, S.R., 2007. An androgen-IL-6-Stat3 autocrine loop re-routes EGF signal in prostate cancer cells. Mol Cell Endocrinol, 270(1-2):50-56. 


[2] Abate-Shen, C., Shen, M.M., 2000. Molecular genetics of prostate cancer. Genes Develop, 14(19):2410-2434. 


[3] Abdulghani, J., Gu, L., Dagvadorj, A., 2008. Stat3 promotes metastatic progression of prostate cancer. Am J Pathol, 172(6):1717-1728. 


[4] Alaoui-Jamali, M.A., Xu, Y.J., 2006. Proteomic technology for biomarker profiling in cancer: an update. J Zhejiang Univ-Sci B, 7(6):411-420. 


[5] Al-Azayzih, A., Gao, F., Goc, A., 2012. TGFβ1 induces apoptosis in invasive prostate cancer and bladder cancer cells via Akt-independent, p38 MAPK and JNK/SAPK-mediated activation of caspases. Biochem Biophys Res Commun, 427(1):165-170. 


[6] Al-Maghrebi, M., Kehinde, E.O., Anim, J.T., 2012. The role of combined measurement of tissue mRNA levels of AMACR and survivin in the diagnosis and risk stratification of patients with suspected prostate cancer. Int Urol Nephrol, 44(6):1681-1689. 


[7] Almasi, C.E., Brasso, K., Iversen, P., 2011. Prognostic and predictive value of intact and cleaved forms of the urokinase plasminogen activator receptor in metastatic prostate cancer. Prostate, 71(8):899-907. 


[8] Amin, M.M., Jeyaganth, S., Fahmy, N., 2007. Subsequent prostate cancer detection in patients with prostatic intraepithelial neoplasia or atypical small acinar proliferation. Can Urol Assoc J, 1(3):245-249. 


[9] Antonarakis, E.S., Eisenberger, M.A., 2011. Expanding treatment options for metastatic prostate cancer. N Engl J Med, 364(21):2055-2058. 


[10] Antonarakis, E.S., Keizman, D., Zhang, Z., 2012. An immunohistochemical signature comprising PTEN, MYC, and Ki67 predicts progression in prostate cancer patients receiving adjuvant docetaxel after prostatectomy. Cancer, 118(24):6063-6071. 


[11] Azevedo, A., Cunha, V., Teixeira, A.L., 2011. IL-6/IL-6R as a potential key signaling pathway in prostate cancer development. World J Clin Oncol, 2(12):384-396. 


[12] Barrack, E.R., 1997. TGFβ in prostate cancer: a growth inhibitor that can enhance tumorigenicity. Prostate, 31(1):61-70. 


[13] Battisti, V., Maders, L.D., Bagatini, M.D., 2011. Oxidative stress and antioxidant status in prostate cancer patients: relation to Gleason score, treatment and bone metastasis. Biomed Pharmacother, 65(7):516-524. 


[14] Bellacosa, A., Larue, L., 2010. PI3K/AKT pathway and the epithelial-mesenchymal transition.  Cancer Genome and Tumor Microenvironment. Springer,New York :11-32. 


[15] Bello-DeOcampo, D., Tindall, D.J., 2003. TGF-β/Smad signaling in prostate cancer. Curr Drug Targets, 4(3):197-207. 


[16] Bernardini, S., Miano, R., Iori, R., 2004. Hypermethylation of the CpG islands in the promoter region of the GSTP1 gene in prostate cancer: a useful diagnostic and prognostic marker?. Clin Chim Acta, 350(1-2):181-188. 


[17] Bhardwaj, A., Singh, S., Srivastava, S.K., 2011. Modulation of protein phosphatase 2A activity alters androgen-independent growth of prostate cancer cells: therapeutic implications. Mol Cancer Ther, 10(5):720-731. 


[18] Bickers, B., Aukim-Hastie, C., 2009. New molecular biomarkers for the prognosis and management of prostate cancer—the post PSA era. Anticancer Res, 29(8):3289-3298. 


[19] Bonkhoff, H., 1998. Analytical molecular pathology of epithelial-stromal interactions in the normal and neoplastic prostate. Anal Quant Cytol Histol, 20(5):437-442. 


[20] Bonkhoff, H., Fixemer, T., Hunsicker, I., 1999. Estrogen receptor expression in prostate cancer and premalignant prostatic lesions. Am J Pathol, 155(2):641-647. 


[21] Borley, N., Feneley, M.R., 2008. Prostate cancer: diagnosis and staging. Asian J Androl, 11(1):74-80. 


[22] Bostwick, D.G., 1989. The pathology of early prostate cancer. CA Cancer J Clin, 39(6):376-393. 


[23] Bostwick, D.G., Brawer, M.K., 1987. Prostatic intra-epithelial neoplasia and early invasion in prostate cancer. Cancer, 59(4):788-794. 


[24] Bostwick, D.G., Pacelli, A., Lopez-Beltran, A., 1996. Molecular biology of prostatic intraepithelial neoplasia. Prostate, 29(2):117-134. 


[25] Boyd, L.K., Mao, X., Lu, Y.J., 2012. The complexity of prostate cancer: genomic alterations and heterogeneity. Nat Rev Urol, 9(11):652-664. 


[26] Brand, T.C., Bermejo, C., Canby-Hagino, E., 2008. Association of polymorphisms in TGFB1 and prostate cancer prognosis. J Urol, 179(2):754-758. 


[27] Brodin, G., Dijke, P.T., Funa, K., 1999. Increased Smad expression and activation are associated with apoptosis in normal and malignant prostate after castration. Cancer Res, 59(11):2731-2738. 


[28] Bryzgunova, O.E., Morozkin, E.S., Yarmoschuk, S.V., 2008. Methylation-specific sequencing of GSTP1 gene promoter in circulating/extracellular DNA from blood and urine of healthy donors and prostate cancer patients. Ann N Y Acad Sci, 1137(1):222-225. 


[29] Bubendorf, L., Schopfer, A., Wagner, U., 2000. Metastatic patterns of prostate cancer: an autopsy study of 1589 patients. Hum Pathol, 31(5):578-583. 


[30] Buchanan, G., Greenberg, N.M., Scher, H.I., 2001. Collocation of androgen receptor gene mutations in prostate cancer. Clin Cancer Res, 7(5):1273-1281. 


[31] Bussemakers, M.J., van Bokhoven, A., Verhaegh, G.W., 1999. DD3: a new prostate-specific gene, highly overexpressed in prostate cancer. Cancer Res, 59(23):5975-5979. 


[32] Carruba, G., 2007. Estrogen and prostate cancer: an eclipsed truth in an androgen-dominated scenario. J Cell Biochem, 102(4):899-911. 


[33] Cavalieri, E.L., Rogan, E.G., 2006. A unified mechanism in the initiation of cancer. Ann N Y Acad Sci, 959:341-354. 


[34] Chan, S.C., Li, Y.M., Dehm, S.M., 2012. Androgen receptor splice variants activate androgen receptor target genes and support aberrant prostate cancer cell growth independent of canonical androgen receptor nuclear localization signal. J Biol Chem, 287(23):19736-19749. 


[35] Chen, C.L., Mahalingam, D., Osmulski, P., 2013. Single-cell analysis of circulating tumor cells identifies cumulative expression patterns of EMT-related genes in metastatic prostate cancer. Prostate, 73(8):813-826. 


[36] Chen, J., De, S., Brainard, J., 2004. Metastatic properties of prostate cancer cells are controlled by VEGF. Cell Commun Adhes, 11(1):1-11. 


[37] Chen, S., Kesler, C.T., Paschal, B.M., 2009. Androgen receptor phosphorylation and activity are regulated by an association with protein phosphatase 1. J Biol Chem, 284(38):25576-25584. 


[38] Chen, Y., Li, J., Yu, X., 2013. APC gene hypermethylation and prostate cancer: a systematic review and meta-analysis. Eur J Hum Genet, 21(9):929-935. 


[39] Chen, Z., Trotman, L.C., Shaffer, D., 2005. Crucial role of p53-dependent cellular senescence in suppression of Pten-deficient tumorigenesis. Nature, 436(7051):725-730. 


[40] Chetram, M.A., Odero-Marah, V., Hinton, C.V., 2011. Loss of PTEN permits CXCR4-mediated tumorigenesis through ERK1/2 in prostate cancer cells. Mol Cancer Res, 9(1):90-102. 


[41] Choucair, K., Ejdelman, J., Brimo, F., 2012. PTEN genomic deletion predicts prostate cancer recurrence and is associated with low AR expression and transcriptional activity. BMC Cancer, 12(1):543


[42] Clarke, N.W., Hart, C.A., Brown, M.D., 2009. Molecular mechanisms of metastasis in prostate cancer. Asian J Androl, 11(1):57-67. 


[43] Coleman, K.M., Smith, C.L., 2001. Intracellular signaling pathways: nongenomic actions of estrogens and ligand-independent activation of estrogen receptors. Front Biosci, 6(1):D1379-D1391. 


[44] Committee on Developing Biomarker-Based Tools for Cancer Screening, Diagnosis, and Treatment, 2007. Methods, tools, and resources needed to discover and develop biomarkers.  Cancer Biomarkers: The Promises and Challenges of Improving Detection and Treatment. National Academies Press,Washington, DC :

[45] Craft, C.S., Romero, D., Vary, C.P., 2007. Endoglin inhibits prostate cancer motility via activation of the ALK2-Smad1 pathway. Oncogene, 26(51):7240-7250. 


[46] Craft, N., Shostak, Y., Carey, M., 1999. A mechanism for hormone-independent prostate cancer through modulation of androgen receptor signaling by the HER-2/neu tyrosine kinase. Nat Med, 5(3):280-285. 


[47] Crawford, E.D., 2009. Understanding the epidemiology, natural history, and key pathways involved in prostate cancer. Urology, 73(5 Suppl.):S4-S10. 


[48] Crawford, E.D., Rove, K.O., Trabulsi, E.J., 2012. Diagnostic performance of PCA3 to detect prostate cancer in men with increased prostate specific antigen: a prospective study of 1962 cases. J Urol, 188(5):1726-1731. 


[49] Dai, J., Keller, J., Zhang, J., 2005. Bone morphogenetic protein-6 promotes osteoblastic prostate cancer bone metastases through a dual mechanism. Cancer Res, 65(18):8274-8285. 


[50] Danila, D.C., Anand, A., Sung, C.C., 2011. TMPRSS2-ERG status in circulating tumor cells as a predictive biomarker of sensitivity in castration-resistant prostate cancer patients treated with abiraterone acetate. Eur Urol, 60(5):897-904. 


[51] Darby, S., Cross, S.S., Brown, N.J., 2008. BMP-6 over-expression in prostate cancer is associated with increased Id-1 protein and a more invasive phenotype. J Pathol, 214(3):394-404. 


[52] Darson, M.F., Pacelli, A., Roche, P., 1997. Human glandular kallikrein 2 (hK2) expression in prostatic intraepithelial neoplasia and adenocarcinoma: a novel prostate cancer marker. Urology, 49(6):857-862. 


[53] Davidsson, S., Fiorentino, M., Andren, O., 2011. Inflammation, focal atrophic lesions, and prostatic intraepithelial neoplasia with respect to risk of lethal prostate cancer. Cancer Epidemiol Biomarkers Prev, 20(10):2280-2287. 


[54] de Marzo, A.M., Marchi, V.L., Epstein, J.I., 1999. Proliferative inflammatory atrophy of the prostate: implications for prostatic carcinogenesis. Am J Pathol, 155(6):1985-1992. 


[55] Derynck, R., Feng, X.H., 1997. TGF-β receptor signaling. Biochim Biophys Acta, 1333(2):F105-F150. 


[56] Djulbegovic, M., Beyth, R.J., Neuberger, M.M., 2010. Screening for prostate cancer: systematic review and meta-analysis of randomised controlled trials. BMJ, 14(341):c4543


[57] Donaldson, L., Fordyce, C., Gilliland, F., 1999. Association between outcome and telomere DNA content in prostate cancer. J Urol, 162(5):1788-1792. 


[58] Drudge-Coates, L., Turner, B., 2012. Prostate cancer overview. Part 2: metastatic prostate cancer. Brit J Nurs, 21(18):S23-S24. 

[59] Dubrovska, A., Kim, S., Salamone, R.J., 2009. The role of PTEN/Akt/PI3K signaling in the maintenance and viability of prostate cancer stem-like cell populations. PNAS, 106(1):268-273. 


[60] Edlund, S., Bu, S., Schuster, N., 2003. Transforming growth factor-β1 (TGF-β)-induced apoptosis of prostate cancer cells involves Smad7-dependent activation of p38 by TGF-β-activated kinase 1 and mitogen-activated protein kinase kinase 3. Mol Biol Cell, 14(2):529-544. 


[61] Ellem, S.J., Schmitt, J.F., Pedersen, J.S., 2004. Local aromatase expression in human prostate is altered in malignancy. J Clin Endocrinol Metab, 89(5):2434-2441. 


[62] European Medicines Agency, 2009. Firmagon, Available from ,:

[63] European Medicines Agency, 2011. Jevtana, Available from ,:

[64] European Medicines Agency, 2011. Zytiga, Available from ,:

[65] Ewald, J.A., Desotelle, J.A., Church, D.R., 2013. Androgen deprivation induces senescence characteristics in prostate cancer cells in vitro and in vivoProstate, 73(4):337-345. 


[66] Fardilha, M., Esteves, S.L.C., Korrodi-Gregorio, L., 2010. The physiological relevance of protein phosphatase 1 and its interacting proteins to health and disease. Curr Med Chem, 17(33):3996-4017. 


[67] Fardilha, M., Esteves, S.L., Korrodi-Gregorio, L., 2011. Identification of the human testis protein phosphatase 1 interactome. Biochem Pharmacol, 82(10):1403-1415. 


[68] Faria, P.C., Saba, K., Neves, A.F., 2007. Transforming growth factor-beta 1 gene polymorphisms and expression in the blood of prostate cancer patients. Cancer Invest, 25(8):726-732. 


[69] Feldman, B.J., Feldman, D., 2001. The development of androgen-independent prostate cancer. Nat Rev Cancer, 1(1):34-45. 


[70] Feng, S., Dakhova, O., Creighton, C.J., 2013. The endocrine fibroblast growth factor FGF19 promotes prostate cancer progression. Cancer Res, 73(8):2551-2562. 


[71] Ferlay, J., Parkin, D.M., Steliarova-Foucher, E., 2010. Estimates of cancer incidence and mortality in Europe in 2008. Eur J Cancer, 46(4):765-781. 


[72] Ferreira, L.B., Palumbo, A., de Mello, K.D., 2012. PCA3 noncoding RNA is involved in the control of prostate-cancer cell survival and modulates androgen receptor signaling. BMC Cancer, 12:507


[73] Ferrer, F.A., Miller, L.J., Andrawis, R.I., 1997. Vascular endothelial growth factor (VEGF) expression in human prostate cancer: in situ and in vitro expression of VEGF by human prostate cancer cells. J Urol, 157(6):2329-2333. 


[74] Festuccia, C., Bologna, M., Gravina, G.L., 1999. Osteoblast conditioned media contain TGF-β1 and modulate the migration of prostate tumor cells and their interactions with extracellular matrix components. Int J Cancer, 81(3):395-403. 


[75] Fisher, G., Yang, Z.H., Kudahetti, S., 2013. Prognostic value of Ki-67 for prostate cancer death in a conservatively managed cohort. Brit J Cancer, 108(2):271-277. 


[76] Fixemer, T., Remberger, K., Bonkhoff, H., 2003. Differential expression of the estrogen receptor beta (ERβ) in human prostate tissue, premalignant changes, and in primary, metastatic, and recurrent prostatic adenocarcinoma. Prostate, 54(2):79-87. 


[77] Fordyce, C.A., Heaphy, C.M., Joste, N.E., 2005. Association between cancer-free survival and telomere DNA content in prostate tumors. J Urol, 173(2):610-614. 


[78] Foster, C.S., Bostwick, D.G., Bonkhoff, H., 2000. Cellular and molecular pathology of prostate cancer precursors. Scand J Urol Nephrol Suppl, 34(1):19-43. 


[79] Gabel, S., Benefield, J., Meisinger, J., 1999. Protein phosphatases 1 and 2A maintain endothelial cells in a resting state, limiting the motility that is needed for the morphogenic process of angiogenesis. Otolaryngol Head Neck Surg, 121(4):463-468. 


[80] Gao, J., Arnold, J.T., Isaacs, J.T., 2001. Conversion from a paracrine to an autocrine mechanism of androgen-stimulated growth during malignant transformation of prostatic epithelial cells. Cancer Res, 61(13):5038-5044. 


[81] Gao, N., Zhang, Z., Jiang, B.H., 2003. Role of PI3K/AKT/mTOR signaling in the cell cycle progression of human prostate cancer. Biochem Biophys Res Commun, 310(4):1124-1132. 


[82] Gao, X., Zacharek, A., Grignon, D., 1995. High-frequency of loss of expression and allelic deletion of the apc and mcc genes in human prostate-cancer. Int J Oncol, 6(1):111-117. 


[83] Garnero, P., 2001. Markers of bone turnover in prostate cancer. Cancer Treat Rev, Discussion 193-186,27(3):187-192. 


[84] Garnero, P., Buchs, N., Zekri, J., 2000. Markers of bone turnover for the management of patients with bone metastases from prostate cancer. Brit J Cancer, 82(4):858-864. 


[85] Gnanapragasam, V.J., Robson, C.N., Neal, D.E., 2002. Regulation of FGF8 expression by the androgen receptor in human prostate cancer. Oncogene, 21(33):5069-5080. 


[86] Goc, A., Al-Husein, B., Kochuparambil, S.T., 2011. PI3 kinase integrates Akt and MAP kinase signaling pathways in the regulation of prostate cancer. Int J Oncol, 38(1):267-277. 


[87] Goel, M.M., Agrawal, D., Natu, S.M., 2011. Hepsin immunohistochemical expression in prostate cancer in relation to Gleason’s grade and serum prostate specific antigen. Indian J Pathol Microbiol, 54(3):476-481. 


[88] Goering, W., Kloth, M., Schulz, W.A., 2012. DNA methylation changes in prostate cancer. Methods Mol Biol, 863:47-66. 


[89] Gordanpour, A., Nam, R.K., Sugar, L., 2012. MicroRNAs in prostate cancer: from biomarkers to molecularly-based therapeutics. Prostate Cancer Prostatic Dis, 15(4):314-319. 


[90] Grignon, D.J., 2004. Unusual subtypes of prostate cancer. Modern Pathol, 17(3):316-327. 


[91] Gu, L., Dagvadorj, A., Lutz, J., 2010. Transcription factor Stat3 stimulates metastatic behavior of human prostate cancer cells in vivo, whereas Stat5b has a preferential role in the promotion of prostate cancer cell viability and tumor growth. Am J Pathol, 176(4):1959-1972. 


[92] Gueron, G., de Siervi, A., Vazquez, E., 2012. Advanced prostate cancer: reinforcing the strings between inflammation and the metastatic behavior. Prostate Cancer Prostatic Dis, 15(3):213-221. 


[93] Guo, Y., Jacobs, S.C., Kyprianou, N., 1997. Down-regulation of protein and mRNA expression for transforming growth factor-β (TGF-β1) type I and type II receptors in human prostate cancer. Int J Cancer, 71(4):573-579. 


[94] Guo, Z., Yang, X., Sun, F., 2009. A novel androgen receptor splice variant is up-regulated during prostate cancer progression and promotes androgen depletion-resistant growth. Cancer Res, 69(6):2305-2313. 


[95] Gupta-Elera, G., Garrett, A.R., Robison, R.A., 2012. The role of oxidative stress in prostate cancer. Eur J Cancer Prev, 21(2):155-162. 


[96] Haas, G.P., Delongchamps, N.B., Jones, R.F., 2007. Needle biopsies on autopsy prostates: sensitivity of cancer detection based on true prevalence. J Natl Cancer Inst, 99(19):1484-1489. 


[97] Hamdy, F.C., Autzen, P., Robinson, M.C., 1997. Immunolocalization and messenger RNA expression of bone morphogenetic protein-6 in human benign and malignant prostatic tissue. Cancer Res, 57(19):4427-4431. 


[98] Hayes, S.A., Huang, X., Kambhampati, S., 2003. p38 MAP kinase modulates Smad-dependent changes in human prostate cell adhesion. Oncogene, 22(31):4841-4850. 


[99] He, H.C., Bi, X.C., Zheng, Z.W., 2009. Real-time quantitative RT-PCR assessment of PIM-1 and hK2 mRNA expression in benign prostate hyperplasia and prostate cancer. Med Oncol, 26(3):303-308. 


[100] Heemers, H.V., Tindall, D.J., 2007. Androgen receptor (AR) coregulators: a diversity of functions converging on and regulating the AR transcriptional complex. Endocrine Rev, 28(7):778-808. 


[101] Hegele, A., Wahl, H.G., Varga, Z., 2007. Biochemical markers of bone turnover in patients with localized and metastasized prostate cancer. BJU Int, 99(2):330-334. 


[102] Heidenreich, A., Bastian, P.J., Bellmunt, J., 2012. Guidelines on prostate cancer, Available from: http://www.uroweb.org/guidelines/online-guidelines/, European Association of Urology,:35-102. 

[103] Heinlein, C.A., Chang, C., 2004. Androgen receptor in prostate cancer. Endocrine Rev, 25(2):276-308. 


[104] Hrnberg, E., Ylitalo, E.B., Crnalic, S., 2011. Expression of androgen receptor splice variants in prostate cancer bone metastases is associated with castration-resistance and short survival. PLoS ONE, 6(4):e19059


[105] Horvath, L.G., Henshall, S.M., Lee, C.S., 2001. Frequent loss of estrogen receptor-β expression in prostate cancer. Cancer Res, 61(14):5331-5335. 


[106] Horvath, L.G., Henshall, S.M., Kench, J.G., 2004. Loss of BMP2, Smad8, and Smad4 expression in prostate cancer progression. Prostate, 59(3):234-242. 


[107] Huggins, C., Hodges, C.V., 1972. Studies on prostatic cancer: I. The effect of castration, of estrogen and of androgen injection on serum phosphatases in metastatic carcinoma of the prostate. CA Cancer J Clin, 22(4):232-240. 


[108] Ilic, D., OConnor, D., Green, S., 2011. Screening for prostate cancer: an updated Cochrane systematic review. BJU Int, 107(6):882-891. 


[109] Jariwala, U., Prescott, J., Jia, L., 2007. Identification of novel androgen receptor target genes in prostate cancer. Mol Cancer, 6(1):1-15. 


[110] Jemal, A., Bray, F., Center, M.M., 2011. Global cancer statistics. CA Cancer J Clin, 61(2):69-90. 


[111] Jennbacken, K., Vallbo, C., Wang, W., 2005. Expression of vascular endothelial growth factor C (VEGF-C) and VEGF receptor-3 in human prostate cancer is associated with regional lymph node metastasis. Prostate, 65(2):110-116. 


[112] Jiang, Q., Yeh, S., Wang, X., 2012. Targeting androgen receptor leads to suppression of prostate cancer via induction of autophagy. J Urol, 188(4):1361-1368. 


[113] Josefsson, A., Wikstrom, P., Egevad, L., 2012. Low endoglin vascular density and Ki67 index in Gleason score 6 tumours may identify prostate cancer patients suitable for surveillance. Scand J Urol Nephrol, 46(4):247-257. 


[114] Kageyama, Y., Kamata, S., Yonese, J., 1997. Telomere length and telomerase activity in bladder and prostate cancer cell lines. Int J Urol, 4(4):407-410. 


[115] Kang, H.Y., Lin, H.K., Hu, Y.C., 2001. From transforming growth factor-beta signaling to androgen action: identification of Smad3 as an androgen receptor coregulator in prostate cancer cells. PNAS, 98(6):3018-3023. 


[116] Kantoff, P.W., Higano, C.S., Shore, N.D., 2010. Sipuleucel-T immunotherapy for castration-resistant prostate cancer. N Engl J Med, 363(5):411-422. 


[117] Karam, J.A., Svatek, R.S., Karakiewicz, P.I., 2008. Use of preoperative plasma endoglin for prediction of lymph node metastasis in patients with clinically localized prostate cancer. Clin Cancer Res, 14(5):1418-1422. 


[118] Kazma, R., Mefford, J.A., Cheng, I., 2012. Association of the innate immunity and inflammation pathway with advanced prostate cancer risk. PLoS ONE, 7(12):e51680


[119] Kelly, K.A., Setlur, S.R., Ross, R., 2008. Detection of early prostate cancer using a hepsin-targeted imaging agent. Cancer Res, 68(7):2286-2291. 


[120] Kim, I.Y., Ahn, H.J., Lang, S., 1998. Loss of expression of transforming growth factor-β receptors is associated with poor prognosis in prostate cancer patients. Clin Cancer Res, 4(7):1625-1630. 


[121] Kim, J., Bilusic, M., Heery, C., 2012. Therapeutic cancer vaccines in prostate cancer: the quest for intermediate markers of response. Cancers, 4(4):1229-1246. 


[122] Klezovitch, O., Chevillet, J., Mirosevich, J., 2004. Hepsin promotes prostate cancer progression and metastasis. Cancer Cell, 6(2):185-195. 


[123] Knudsen, B.S., Vasioukhin, V., 2010. Mechanisms of prostate cancer initiation and progression.  Advances in Cancer Research. Academic Press,United States of America :

[124] Koca, O., Caliskan, S., Ozturk, M.I., 2011. Significance of atypical small acinar proliferation and high-grade prostatic intraepithelial neoplasia in prostate biopsy. Korean J Urol, 52(11):736-740. 


[125] Korrodi-Gregorio, L., Teixeira, A.L., Medeiros, R., 2012. TGFβ pathway.  Essentials of Cell Signaling. (in Portuguese), Afrontamento,Aveiro :199-234. 

[126] Kuiper, G.G., Enmark, E., Pelto-Huikko, M., 1996. Cloning of a novel receptor expressed in rat prostate and ovary. PNAS, 93(12):5925-5930. 


[127] Kumano, M., Miyake, H., Muramaki, M., 2009. Expression of urokinase-type plasminogen activator system in prostate cancer: correlation with clinicopathological outcomes in patients undergoing radical prostatectomy. Urol Oncol, 27(2):180-186. 


[128] Lakshman, M., Huang, X., Ananthanarayanan, V., 2011. Endoglin suppresses human prostate cancer metastasis. Clin Exp Metast, 28(1):39-53. 


[129] Landstrom, M., Heldin, N.E., Bu, S., 2000. Smad7 mediates apoptosis induced by transforming growth factor β in prostatic carcinoma cells. Curr Biol, 10(9):535-538. 


[130] Langenfeld, E.M., Langenfeld, J., 2004. Bone morphogenetic protein-2 stimulates angiogenesis in developing tumors11NIH K22 grant CA91919-01A1 and UMDNJ foundation to J. Langenfeld. Mol Cancer Res, 2(3):141-149. 


[131] Lee, C., Prins, G.S., Henneberry, M.O., 1981. Effect of estradiol on the rat prostate in the presence and absence of testosterone and pituitary. J Androl, 2(6):293-299. 


[132] Lee, C., Sintich, S.M., Mathews, E.P., 1999. Transforming growth factor-β in benign and malignant prostate. Prostate, 39(4):285-290. 


[133] Leiblich, A., Cross, S.S., Catto, J.W., 2006. Lactate dehydrogenase-B is silenced by promoter hypermethy-lation in human prostate cancer. Oncogene, 25(20):2953-2960. 


[134] Leibowitz-Amit, R., Joshua, A.M., 2012. Targeting the androgen receptor in the management of castration-resistant prostate cancer: rationale, progress, and future directions. Curr Oncol, 19(Suppl. 3):S22-S31. 


[135] Leung, Y.K., Lam, H.M., Wu, S., 2010. Estrogen receptor β2 and β5 are associated with poor prognosis in prostate cancer, and promote cancer cell migration and invasion. Endocr Relat Cancer, 17(3):675-689. 


[136] Leung, Y.K., Lee, M.T., Wang, J., 2010. Post-transcriptional regulation of estrogen receptor β isoforms in prostate cancer. , ENDO2010 92nd Annual Meeting, San Diego, California, :

[137] Li, L., Ren, C.H., Tahir, S.A., 2003. Caveolin-1 maintains activated Akt in prostate cancer cells through scaffolding domain binding site interactions with and inhibition of serine/threonine protein phosphatases PP1 and PP2A. Mol Cell Biol, 23(24):9389-9404. 


[138] Li, L., Ittmann, M.M., Ayala, G., 2005. The emerging role of the PI3-K-Akt pathway in prostate cancer progression. Prostate Cancer Prostatic Dis, 8(2):108-118. 


[139] Li, W., Wang, X., Li, B., 2012. Diagnostic significance of overexpression of Golgi membrane protein 1 in prostate cancer. Urology, 80(4):952.e1-952.e7. 


[140] Lin, H.K., Chen, Z., Wang, G., 2010. Skp2 targeting suppresses tumorigenesis by Arf-p53-independent cellular senescence. Nature, 464(7287):374-379. 


[141] Liu, A.J., Furusato, B., Ravindranath, L., 2007. Quantitative analysis of a panel of gene expression in prostate cancer—with emphasis on NPY expression analysis. J Zhejiang Univ-Sci B, 8(12):853-859. 


[142] Liu, L., Kron, K.J., Pethe, V.V., 2011. Association of tissue promoter methylation levels of APC, TGFβ2, HOXD3 and RASSF1A with prostate cancer progression. Int J Cancer, 129(10):2454-2462. 


[143] Liwei, L., Chunyu, L., Jie, L., 2011. Association between fibroblast growth factor receptor-4 gene polymorphism and risk of prostate cancer: a meta-analysis. Urol Int, 87(2):159-164. 


[144] Lockett, K.L., Hall, M.C., Clark, P.E., 2006. DNA damage levels in prostate cancer cases and controls. Carcinogenesis, 27(6):1187-1193. 


[145] Lonergan, P.E., Tindall, D.J., 2011. Androgen receptor signaling in prostate cancer development and progression. J Carcinogen, 10:20


[146] Lopez, J.I., 2007. Prostate adenocarcinoma detected after high-grade prostatic intraepithelial neoplasia or atypical small acinar proliferation. BJU Int, 100(6):1272-1276. 


[147] Lotan, T.L., Gurel, B., Sutcliffe, S., 2011. PTEN protein loss by immunostaining: analytic validation and prognostic indicator for a high risk surgical cohort of prostate cancer patients. Clin Cancer Res, 17(20):6563-6573. 


[148] Lu, T.L., Huang, Y.F., You, L.R., 2013. Conditionally ablated Pten in prostate basal cells promotes basal-to-luminal differentiation and causes invasive prostate cancer in mice. Am J Pathol, 182(3):975-991. 


[149] Lumen, N., Fonteyne, V., de Meerleer, G., 2012. Screening and early diagnosis of prostate cancer: an update. Acta Clin Belg, 67(4):270-275. 


[150] Ma, Y., Cheng, Q., Ren, Z., 2012. Induction of IGF-1R expression by EGR-1 facilitates the growth of prostate cancer cells. Cancer Lett, 317(2):150-156. 


[151] Madani, S.H., Ameli, S., Khazaei, S., 2011. Frequency of Ki-67 (MIB-1) and P53 expressions among patients with prostate cancer. Indian J Pathol Microbiol, 54(4):688-691. 


[152] Majumder, P.K., Sellers, W.R., 2005. Akt-regulated pathways in prostate cancer. Oncogene, 24(50):7465-7474. 


[153] Mak, P., Leav, I., Pursell, B., 2010. ERβ impedes prostate cancer EMT by destabilizing HIF-1α and inhibiting VEGF-mediated snail nuclear localization: implications for Gleason grading. Cancer Cell, 17(4):319-332. 


[154] Makarov, D.V., Loeb, S., Getzenberg, R.H., 2009. Biomarkers for prostate cancer. Ann Rev Med, 60:139-151. 


[155] Mancuso, P.A., Chabert, C., Chin, P., 2007. Prostate cancer detection in men with an initial diagnosis of atypical small acinar proliferation. BJU Int, 99(1):49-52. 


[156] Marino, M., Galluzzo, P., Ascenzi, P., 2006. Estrogen signaling multiple pathways to impact gene transcription. Curr Genomics, 7(8):497-508. 


[157] Marques, R.B., Dits, N.F., Erkens-Schulze, S., 2011. Modulation of androgen receptor signaling in hormonal therapy-resistant prostate cancer cell lines. PLoS ONE, 6(8):e23144


[158] Martin-Granados, C., Prescott, A.R., van Dessel, N., 2012. A role for PP1/NIPP1 in steering migration of human cancer cells. PLoS ONE, 7(7):e40769


[159] Masuda, H., Fukabori, Y., Nakano, K., 2004. Expression of bone morphogenetic protein-7 (BMP-7) in human prostate. Prostate, 59(1):101-106. 


[160] Mattie, M.D., Benz, C.C., Bowers, J., 2006. Optimized high-throughput microRNA expression profiling provides novel biomarker assessment of clinical prostate and breast cancer biopsies. Mol Cancer, 5:24


[161] McConnell, J.L., Wadzinski, B.E., 2009. Targeting protein serine/threonine phosphatases for drug development. Mol Pharmacol, 75(6):1249-1261. 


[162] McPherson, S.J., Hussain, S., Balanathan, P., 2010. Estrogen receptor-β activated apoptosis in benign hyperplasia and cancer of the prostate is androgen independent and TNFα mediated. PNAS, 107(7):3123-3128. 


[163] Merz, V.W., Arnold, A.M., Studer, U.E., 1994. Differential expression of transforming growth factor-β1 and β3 as well as C-FOS mRNA in normal human prostate, benign prostatic hyperplasia and prostatic cancer. World J Urol, 12(2):96-98. 


[164] Meyer, H.A., Ahrens-Fath, I., Sommer, A., 2004. Novel molecular aspects of prostate carcinogenesis. Biomed Pharmacother, 58(1):10-16. 


[165] Miller, D.C., Hafez, K.S., Stewart, A., 2003. Prostate carcinoma presentation, diagnosis, and staging: an update from the National Cancer Data Base. Cancer, 98(6):1169-1178. 


[166] Mitchell, P.S., Parkin, R.K., Kroh, E.M., 2008. Circulating microRNAs as stable blood-based markers for cancer detection. PNAS, 105(30):10513-10518. 


[167] Miyake, H., Hara, I., Kamidono, S., 2004. Oxidative DNA damage in patients with prostate cancer and its response to treatment. J Urol, 171(4):1533-1536. 


[168] Moore, C.K., Karikehalli, S., Nazeer, T., 2005. Prognostic significance of high grade prostatic intrae-pithelial neoplasia and atypical small acinar proliferation in the contemporary era. J Urol, 173(1):70-72. 


[169] Morgan, T.M., Koreckij, T.D., Corey, E., 2009. Targeted therapy for advanced prostate cancer: inhibition of the PI3K/Akt/mTOR pathway. Curr Cancer Drug Targets, 9(2):237-249. 


[170] Moschos, S.J., Mantzoros, C.S., 2002. The role of the IGF system in cancer: from basic to clinical studies and clinical applications. Oncology, 63(4):317-332. 


[171] Naruse, K., Yamada, Y., Aoki, S., 2007. Lactate dehydrogenase is a prognostic indicator for prostate cancer patients with bone metastasis. Hinyokika Kiyo, 53(5):287-292. 


[172] Nelson, W.G., de Marzo, A.M., Isaacs, W.B., 2003. Prostate cancer. N Engl J Med, 349(4):366-381. 


[173] Nieto, M., Finn, S., Loda, M., 2007. Prostate cancer: re-focusing on androgen receptor signaling. Int J Biochem Cell Biol, 39(9):1562-1568. 


[174] Nyquist, M.D., Dehm, S.M., 2013. Interplay between genomic alterations and androgen receptor signaling during prostate cancer development and progression. Hormones Cancer, 4(2):61-69. 


[175] Ohta, S., Fuse, H., Fujiuchi, Y., 2003. Clinical significance of expression of urokinase-type plasminogen activator in patients with prostate cancer. Anticancer Res, 23(3C):2945-2950. 


[176] Okino, S.T., Pookot, D., Majid, S., 2007. Chromatin changes on the GSTP1 promoter associated with its inactivation in prostate cancer. Mol Carcinogen, 46(10):839-846. 


[177] Okotie, O.T., Roehl, K.A., Han, M., 2007. Characteristics of prostate cancer detected by digital rectal examination only. Urology, 70(6):1117-1120. 


[178] Oudard, S., 2013. Progress in emerging therapies for advanced prostate cancer. Cancer Treatment Rev, 39(3):275-289. 


[179] Pace, G., Pomante, R., Vicentini, C., 2012. Hepsin in the diagnosis of prostate cancer. Minerva Urol Nefrol, 64(2):143-148. 


[180] Parsons, J.K., Gage, W.R., Nelson, W.G., 2001. p63 protein expression is rare in prostate adenocarcinoma: implications for cancer diagnosis and carcinogenesis. Urology, 58(4):619-624. 


[181] Pasder, O., Shpungin, S., Salem, Y., 2006. Downregulation of Fer induces PP1 activation and cell-cycle arrest in malignant cells. Oncogene, 25(30):4194-4206. 


[182] Peehl, D.M., 2005. Primary cell cultures as models of prostate cancer development. Endocrine-Related Cancer, 12(1):19-47. 


[183] Perttu, M.C., Martikainen, P.M., Huhtala, H.S., 2006. Altered levels of Smad2 and Smad4 are associated with human prostate carcinogenesis. Prostate Cancer Prostatic Dis, 9(2):185-189. 


[184] Pollak, M., 2008. Insulin and insulin-like growth factor signalling in neoplasia. Nat Rev Cancer, 8(12):915-928. 


[185] Pourmand, G., Ziaee, A.A., Abedi, A.R., 2007. Role of PTEN gene in progression of prostate cancer. Urol Oncol, 4(2):95-100. 

[186] Putzi, M.J., de Marzo, A.M., 2000. Morphologic transitions between proliferative inflammatory atrophy and high-grade prostatic intraepithelial neoplasia. Urology, 56(5):828-832. 


[187] Qi, L., Robinson, W.A., Brady, B.M., 2003. Migration and invasion of human prostate cancer cells is related to expression of VEGF and its receptors. Anticancer Res, 23(5A):3917-3922. 


[188] Qu, F., Cui, X., Hong, Y., 2013. MicroRNA-185 suppresses proliferation, invasion, migration, and tumorigenicity of human prostate cancer cells through targeting androgen receptor. Mol Cell Biochem, 377(1-2):121-130. 


[189] Raaijmakers, R., Kirkels, W.J., Roobol, M.J., 2002. Complication rates and risk factors of 5802 transrectal ultrasound-guided sextant biopsies of the prostate within a population-based screening program. Urology, 60(5):826-830. 


[190] Raaijmakers, R., de Vries, S.H., Blijenberg, B.G., 2007. hK2 and free PSA, a prognostic combination in predicting minimal prostate cancer in screen-detected men within the PSA range 4–10 ng/ml. Eur Urol, 52(5):1358-1364. 


[191] Reynolds, A.R., Kyprianou, N., 2006. Growth factor signalling in prostatic growth: significance in tumour development and therapeutic targeting. Brit J Pharmacol, 147(S2):S144-S152. 


[192] Rhea, J.M., Molinaro, R.J., 2011. Cancer biomarkers: surviving the journey from bench to bedside. Med Lab Obs, 43(3):10-18. 

[193] Ricke, W.A., McPherson, S.J., Bianco, J.J., 2008. Prostatic hormonal carcinogenesis is mediated by in situ estrogen production and estrogen receptor alpha signaling. FASEB J, 22(5):1512-1520. 


[194] Rolan, P., 1997. The contribution of clinical pharmacology surrogates and models to drug development—a critical appraisal. Brit J Clin Pharmacol, 44(3):219-225. 


[195] Romero, D., Terzic, A., Conley, B.A., 2010. Endoglin phosphorylation by ALK2 contributes to the regulation of prostate cancer cell migration. Carcinogenesis, 31(3):359-366. 


[196] Rubin, M.A., Zhou, M., Dhanasekaran, S.M., 2002. Alpha-methylacyl coenzyme A racemase as a tissue biomarker for prostate cancer. JAMA, 287(13):1662-1670. 


[197] Saez, C., Gonzalez-Baena, A.C., Japon, M.A., 1998. Regressive changes in finasteride-treated human hyperplastic prostates correlate with an upregulation of TGF-β receptor expression. Prostate, 37(2):84-90. 


[198] Salmena, L., Carracedo, A., Pandolfi, P.P., 2008. Tenets of PTEN tumor suppression. Cell, 133(3):403-414. 


[199] Samaratunga, H., Gardiner, R.A., Yaxley, J., 2006. Atypical prostatic glandular proliferations on needle biopsy: diagnostic implications, use of immunohistochemistry, and clinical significance. Anal Quant Cytol Histol, 28(2):104-110. 


[200] Schindl, M., Oberhuber, G., Obermair, A., 2001. Overexpression of Id-1 protein is a marker for unfavorable prognosis in early-stage cervical cancer. Cancer Res, 61(15):5703-5706. 


[201] Schindl, M., Schoppmann, S.F., Strobel, T., 2003. Level of Id-1 protein expression correlates with poor differentiation, enhanced malignant potential, and more aggressive clinical behavior of epithelial ovarian tumors. Clin Cancer Res, 9(2):779-785. 


[202] Schrder, F.H., Gosselaar, C., Roemeling, S., 2006. PSA and the detection of prostate cancer after 2005. Part I. EAU-EBU Update Series, 4(1):2-12. 

[203] Sfanos, K.S., de Marzo, A.M., 2012. Prostate cancer and inflammation: the evidence. Histopathology, 60(1):199-215. 


[204] Shi, W., Sun, C., He, B., 2004. GADD34-PP1c recruited by Smad7 dephosphorylates TGFβ type I receptor. J Cell Biol, 164(2):291-300. 


[205] Shteynshlyuger, A., Andriole, G.L., 2010. Prostate cancer: to screen or not to screen?. Urol Clin N Am, 37(1):1-9. 


[206] Singh, P.B., Matanhelia, S.S., Martin, F.L., 2008. A potential paradox in prostate adenocarcinoma progression: oestrogen as the initiating driver. Eur J Cancer, 44(7):928-936. 


[207] Smith, R.A., Mettlin, C.J., Eyre, H., 2003. Cancer screening and early detection.  Holland-Frei Cancer Medicine. BC Decker,Canada :

[208] Som, A., Tu, S.M., Liu, J., 2012. Response in bone turnover markers during therapy predicts overall survival in patients with metastatic prostate cancer: analysis of three clinical trials. Brit J Cancer, 107(9):1547-1553. 


[209] Soulitzis, N., Karyotis, I., Delakas, D., 2006. Expression analysis of peptide growth factors VEGF, FGF2, TGFB1, EGF and IGF1 in prostate cancer and benign prostatic hyperplasia. Int J Oncol, 29(2):305-314. 


[210] Squire, J.A., 2009. TMPRSS2-ERG and PTEN loss in prostate cancer. Nat Genet, 41(5):509-510. 


[211] Stamey, T.A., Johnstone, I.M., McNeal, J.E., 2002. Preoperative serum prostate specific antigen levels between 2 and 22 ng/ml correlate poorly with post-radical prostatectomy cancer morphology: prostate specific antigen cure rates appear constant between 2 and 9 ng/ml. J Urol, 167(1):103-111. 


[212] Stattin, P., Rinaldi, S., Biessy, C., 2004. High levels of circulating insulin-like growth factor-I increase prostate cancer risk: a prospective study in a population-based nonscreened cohort. J Clin Oncol, 22(15):3104-3112. 


[213] Steuber, T., Vickers, A.J., Serio, A.M., 2007. Comparison of free and total forms of serum human kallikrein 2 and prostate-specific antigen for prediction of locally advanced and recurrent prostate cancer. Clin Chem, 53(2):233-240. 


[214] Szczyrba, J., Nolte, E., Wach, S., 2011. Downregulation of Sec23A protein by miRNA-375 in prostate carcinoma. Mol Cancer Res, 9(6):791-800. 


[215] Taira, J., Higashimoto, Y., 2013. Caveolin-1 interacts with protein phosphatase 5 and modulates its activity in prostate cancer cells. Biochem Biophys Res Commun, 431(4):724-728. 


[216] Teishima, J., Shoji, K., Hayashi, T., 2012. Relationship between the localization of fibroblast growth factor 9 in prostate cancer cells and postoperative recurrence. Prostate Cancer Prostatic Dis, 15(1):8-14. 


[217] Thalgott, M., Rack, B., Maurer, T., 2013. Detection of circulating tumor cells in different stages of prostate cancer. J Cancer Res Clin Oncol, 139(5):755-763. 


[218] Thara, E., Dorff, T.B., Pinski, J.K., 2011. Vaccine therapy with sipuleucel-T (Provenge) for prostate cancer. Maturitas, 69(4):296-303. 


[219] Tomlins, S.A., Rhodes, D.R., Perner, S., 2005. Recurrent fusion of TMPRSS2 and ETS transcription factor genes in prostate cancer. Science, 310(5748):644-648. 


[220] Treat, E.G., Heaphy, C.M., Massie, L.W., 2010. Telomere DNA content in prostate biopsies predicts early rise in prostate-specific antigen after radical prostatectomy for prostate cancer. Urology, 75(3):724-729. 


[221] Trojan, L., Thomas, D., Knoll, T., 2004. Expression of pro-angiogenic growth factors VEGF, EGF and bFGF and their topographical relation to neovascularisation in prostate cancer. Urol Res, 32(2):97-103. 


[222] Tu, W.H., Thomas, T.Z., Masumori, N., 2003. The loss of TGF-β signaling promotes prostate cancer metastasis. Neoplasia, 5(3):267-277. 


[223] Turner, B.J., Mavandadi, S., Weiner, M.G., 2011. Association of black race with follow-up of an abnormal prostate-specific antigen test. J Natl Med Assoc, 103(2):150-157. 


[224] US Food and Drug Administration, 2010. Provenge, Available from http://www.fda.gov/BiologicsBloodVaccines/CellularGeCeTherapyProducts/ApprovedProducts/ucm210012.htm, US Food and Drug Administration,:

[225] Vandenboom Ii, T.G., Li, Y., Philip, P.A., 2008. MicroRNA and cancer: tiny molecules with major implications. Curr Genomics, 9(2):97-109. 


[226] Vander Griend, D.J., D'Antonio, J., Gurel, B., 2010. Cell-autonomous intracellular androgen receptor signaling drives the growth of human prostate cancer initiating cells. Prostate, 70(1):90-99. 


[227] Varambally, S., Laxman, B., Mehra, R., 2008. Golgi protein GOLM1 is a tissue and urine biomarker of prostate cancer. Neoplasia, 10(11):1285-1294. 


[228] Vo, B.T., Khan, S.A., 2011. Expression of nodal and nodal receptors in prostate stem cells and prostate cancer cells: autocrine effects on cell proliferation and migration. Prostate, 71(10):1084-1096. 


[229] Wang, H., Fan, L., Wei, J., 2012. Akt mediates metastasis-associated gene 1 (MTA1) regulating the expression of E-cadherin and promoting the invasiveness of prostate cancer cells. PLoS ONE, 7(12):e46888


[230] Wang, J., Yu, W., Cai, Y., 2008. Altered fibroblast growth factor receptor 4 stability promotes prostate cancer progression. Neoplasia, 10(8):847-856. 


[231] Wang, W., Bergh, A., Damber, J.E., 2009. Morphological transition of proliferative inflammatory atrophy to high-grade intraepithelial neoplasia and cancer in human prostate. Prostate, 69(13):1378-1386. 


[232] Wikstrom, P., Lissbrant, I.F., Stattin, P., 2002. Endoglin (CD105) is expressed on immature blood vessels and is a marker for survival in prostate cancer. Prostate, 51(4):268-275. 


[233] Wilt, T.J., Shamliyan, T., Taylor, B., 2008. Comparative effectiveness of therapies for clinically localized prostate cancer.  AHRQ Comparative Effectiveness Reviews. Rockville,United States of America :

[234] Woodson, K., O'Reilly, K.J., Hanson, J.C., 2008. The usefulness of the detection of GSTP1 methylation in urine as a biomarker in the diagnosis of prostate cancer. J Urol, Discussion 511-502,179(2):508-511. 


[235] Wu, Z., McRoberts, K.S., Theodorescu, D., 2007. The role of PTEN in prostate cancer cell tropism to the bone micro-environment. Carcinogenesis, 28(7):1393-1400. 


[236] Wu, Z., He, B., He, J., 2012. Upregulation of miR-153 promotes cell proliferation via downregulation of the PTEN tumor suppressor gene in human prostate cancer. Prostate, 73(6):596-604. 


[237] Xu, T., He, K., Wang, L., 2011. Prostate tumor cells with cancer progenitor properties have high telomerase activity and are rapidly killed by telomerase interference. Prostate, 71(13):1390-1400. 


[238] Yager, J.D., 2000. Endogenous estrogens as carcinogens through metabolic activation. J Natl Cancer Inst Monogr, 2000(27):67-73. 

[239] Yaman Agaoglu, F., Kovancilar, M., Dizdar, Y., 2011. Investigation of miR-21, miR-141, and miR-221 in blood circulation of patients with prostate cancer. Tumour Biol, 32(3):583-588. 


[240] Yang, F., Strand, D.W., Rowley, D.R., 2008. Fibroblast growth factor-2 mediates transforming growth factor-β action in prostate cancer reactive stroma. Oncogene, 27(4):450-459. 


[241] Yang, Q., Fung, K.M., Day, W.V., 2005. Androgen receptor signaling is required for androgen-sensitive human prostate cancer cell proliferation and survival. Cancer Cell Int, 5(1):8


[242] Yang, X., Guo, Z., Sun, F., 2011. Novel membrane-associated androgen receptor splice variant potentiates proliferative and survival responses in prostate cancer cells. J Biol Chem, 286(41):36152-36160. 


[243] Yap, T.A., Swanton, C., de Bono, J.S., 2012. Personalization of prostate cancer prevention and therapy: are clinically qualified biomarkers in the horizon?. EPMA J, 3(1):3


[244] Ye, L., Lewis-Russell, J.M., Kyanaston, H.G., 2007. Bone morphogenetic proteins and their receptor signaling in prostate cancer. Histol Histopathol, 22(10):1129-1147. 


[245] Ye, L., Lewis-Russell, J.M., Kynaston, H., 2007. Endogenous bone morphogenetic protein-7 controls the motility of prostate cancer cells through regulation of bone morphogenetic protein antagonists. J Urol, 178(3 Pt 1):1086-1091. 


[246] Ye, L., Kynaston, H., Jiang, W.G., 2008. Bone morphogenetic protein-9 induces apoptosis in prostate cancer cells, the role of prostate apoptosis response-4. Mol Cancer Res, 6(10):1594-1606. 


[247] Ye, L., Kynaston, H., Jiang, W.G., 2009. Bone morphogenetic protein-10 suppresses the growth and aggressiveness of prostate cancer cells through a Smad independent pathway. J Urol, 181(6):2749-2759. 


[248] Yoon, H.Y., Kim, S.K., Kim, Y.W., 2012. Combined hypermethylation of APC and GSTP1 as a molecular marker for prostate cancer: quantitative pyrosequencing analysis. J Biomol Screen, 17(7):987-992. 


[249] Yuen, H.F., Chan, Y.P., Cheung, W.L., 2008. The prognostic significance of BMP-6 signaling in prostate cancer. Modern Pathol, 21(12):1436-1443. 


[250] Yutkin, V., Al-Zahrani, A., Williams, A., 2012. Pca3 test as an adjunct in diagnosis of prostate cancer. J Urol, 187(4):E889-E889. 

[251] Zhao, Z., Zeng, G., Zhong, W., 2010. Serum early prostate cancer antigen (EPCA) as a significant predictor of incidental prostate cancer in patients undergoing transurethral resection of the prostate for benign prostatic hyperplasia. Prostate, 70(16):1788-1798. 


[252] Zhao, Z., Ma, W., Zeng, G., 2012. Preoperative serum levels of early prostate cancer antigen (EPCA) predict prostate cancer progression in patients undergoing radical prostatectomy. Prostate, 72(3):270-279. 


[253] Zhou, X., Mao, J., Ai, J., 2012. Identification of plasma lipid biomarkers for prostate cancer by lipidomics and bioinformatics. PLoS ONE, 7(11):e48889


[254] Zhu, M.L., Kyprianou, N., 2008. Androgen receptor and growth factor signaling cross-talk in prostate cancer cells. Endocrine-Related Cancer, 15(4):841-849. 



Open peer comments: Debate/Discuss/Question/Opinion

<1>

YI@No address<No mail>

2014-02-08 10:58:25

This is an excellent review for recent progress in the molecular pathology of prostate cancer. I believe that this article would give high impact to the wide range of fields of clinical and/or biological sciences.

MM@No address<No mail>

2014-02-08 10:56:36

In this review Authors describe the pathophysiological features of PCa focusing in the main molecular processes involved the conventional approaches to PCa diagnosis and treatment as well as the recent advances in the establishment of new molecular markers for PCa management. The review is well written interesting and well done covering hot issues on PCa.

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