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CLC number: R392.11

On-line Access: 2019-01-07

Received: 2018-04-07

Revision Accepted: 2018-07-08

Crosschecked: 2019-01-02

Cited: 0

Clicked: 3250

Citations:  Bibtex RefMan EndNote GB/T7714

 ORCID:

Wen-bo Ren

https://orcid.org/0000-0002-1638-9343

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Journal of Zhejiang University SCIENCE B 2019 Vol.20 No.1 P.39-48

http://doi.org/10.1631/jzus.B1800211


Interferon-γ regulates cell malignant growth via the c-Abl/HDAC2 signaling pathway in mammary epithelial cells


Author(s):  Wen-bo Ren, Xiao-jing Xia, Jing Huang, Wen-fei Guo, Yan-yi Che, Ting-hao Huang, Lian-cheng Lei

Affiliation(s):  College of Veterinary Medicine, Jilin University, Changchun 130062, China; more

Corresponding email(s):   leilc@jlu.edu.cn, leiliancheng@163.com

Key Words:  Interferon-γ, (IFN-γ, ), Cellular-abelsongene (c-Abl), Histone deacetylase 2 (HDAC2), Malignant cell growth


Wen-bo Ren, Xiao-jing Xia, Jing Huang, Wen-fei Guo, Yan-yi Che, Ting-hao Huang, Lian-cheng Lei. Interferon-γ regulates cell malignant growth via the c-Abl/HDAC2 signaling pathway in mammary epithelial cells[J]. Journal of Zhejiang University Science B, 2019, 20(1): 39-48.

@article{title="Interferon-γ regulates cell malignant growth via the c-Abl/HDAC2 signaling pathway in mammary epithelial cells",
author="Wen-bo Ren, Xiao-jing Xia, Jing Huang, Wen-fei Guo, Yan-yi Che, Ting-hao Huang, Lian-cheng Lei",
journal="Journal of Zhejiang University Science B",
volume="20",
number="1",
pages="39-48",
year="2019",
publisher="Zhejiang University Press & Springer",
doi="10.1631/jzus.B1800211"
}

%0 Journal Article
%T Interferon-γ regulates cell malignant growth via the c-Abl/HDAC2 signaling pathway in mammary epithelial cells
%A Wen-bo Ren
%A Xiao-jing Xia
%A Jing Huang
%A Wen-fei Guo
%A Yan-yi Che
%A Ting-hao Huang
%A Lian-cheng Lei
%J Journal of Zhejiang University SCIENCE B
%V 20
%N 1
%P 39-48
%@ 1673-1581
%D 2019
%I Zhejiang University Press & Springer
%DOI 10.1631/jzus.B1800211

TY - JOUR
T1 - Interferon-γ regulates cell malignant growth via the c-Abl/HDAC2 signaling pathway in mammary epithelial cells
A1 - Wen-bo Ren
A1 - Xiao-jing Xia
A1 - Jing Huang
A1 - Wen-fei Guo
A1 - Yan-yi Che
A1 - Ting-hao Huang
A1 - Lian-cheng Lei
J0 - Journal of Zhejiang University Science B
VL - 20
IS - 1
SP - 39
EP - 48
%@ 1673-1581
Y1 - 2019
PB - Zhejiang University Press & Springer
ER -
DOI - 10.1631/jzus.B1800211


Abstract: 
interferon-γ; (IFN-γ;) has been used to control cancers in clinical treatment. However, an increasing number of reports have suggested that in some cases effectiveness declines after a long treatment period, the reason being unclear. We have reported previously that long-term IFN-γ treatment induces malignant transformation of healthy lactating bovine mammary epithelial cells (BMECs) in vitro. In this study, we investigated the mechanisms underlying the malignant proliferation of BMECs under IFN-γ treatment. The primary BMECs used in this study were stimulated by IFN-γ (10 ng/mL) for a long term to promote malignancy. We observed that IFN-γ could promote malignant cell proliferation, increase the expression of cyclin D1/cyclin-dependent kinase 4 (CDK4), decrease the expression of p21, and upregulate the expression of cellular-abelsongene (c-Abl) and histone deacetylase 2 (HDAC2). The HDAC2 inhibitor, valproate (VPA) and the c-Abl inhibitor, imatinib, lowered the expression level of cyclin D1/CDK4, and increased the expression level of p21, leading to an inhibitory effect on IFN-γ-induced malignant cell growth. When c-Abl was downregulated, the HDAC2 level was also decreased by promoted proteasome degradation. These data suggest that IFN-γ promotes the growth of malignant BMECs through the c-Abl/HDAC2 signaling pathway. Our findings suggest that long-term application of IFN-γ may be closely associated with the promotion of cell growth and even the carcinogenesis of breast cancer.

γ干扰素通过c-Abl/HDAC2信号通路调节乳腺上皮细胞恶性生长

目的:在之前的研究中我们发现γ干扰素(IFN-γ)通过营养感受器GCN2诱导牛乳腺上皮细胞(BMEC)的恶性转化.在恶性转化的表型中,包括细胞周期缩短、细胞增殖增加、细胞迁移和侵袭的发生,而细胞生长的异常调节是细胞恶性转化的第一步.因此,本研究旨在探讨IFN-γ诱导细胞恶性生长的分子机制.
创新点:实验对象γ-BMEC能够更好的用于乳腺癌发生的基础研究,是一种新的研究工具.我们选择恶性细胞生长来详细研究IFN-γ的作用机制,为IFN-γ、恶性细胞生长甚至乳腺癌之间的密切关系提供直接证据.
方法:通过MTT实验检测IFN-γ长期刺激下细胞的增殖能力;蛋白质印迹(Western blot)检测cyclin D1/CDK4、p21、HDAC2、c-Abl蛋白的表达;免疫荧光观察c-Abl入核.
结论:IFN-γ通过c-Abl/HDAC2信号通路促进恶性BMEC的生长.

关键词:γ干扰素;c-Abl;HDAC2;细胞恶性生长

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

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