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Abstract: Objective: The novel estrogen receptor-α (ER-α) variant ER-α36 is reported to be functional in the estrogen signaling pathway and is related to tamoxifen resistance in breast cancer. However, ER-α36 tends to be a favorable factor for survival in patients without tamoxifen therapy. To investigate the mechanisms behind this paradox, we determined the differences between the transcriptional profiles of ER-α36 and full-length ER-α (ER-α66) in breast cancers and matched normal tissues. Methods: We analyzed ER-α36 and ER-α66 messenger RNA (mRNA) levels in 74 pairs of breast cancers and matched normal tissues using a real-time quantitative polymerase chain reaction (PCR) assay, and correlated the results with their clinicopathological characteristics. Results: breast cancers expressed lower ER-α36 mRNA levels than matched normal tissues regardless of their ER-α66 expression status. Down-regulation of ER-α36 mRNA was correlated with local progression, lymph node metastasis, and advanced cancer stage. The level of ER-α66 mRNA was lower in ER-α negative breast cancers compared with matched normal tissues. No differences in ER-α66 mRNA levels were observed during cancer progression. Conclusion: Down-regulation of ER-α36 is associated with carcinogenesis and progression of breast cancer.

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