Abstract
OBJECTIVE: The novel estrogen receptor-alpha (ER-alpha) variant ER-alpha36 is reported to be functional in the estrogen signaling pathway and is related to tamoxifen resistance in breast cancer. However, ER-alpha36 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-alpha36 and full-length ER-alpha (ER-alpha66) in breast cancers and matched normal tissues. METHODS: We analyzed ER-alpha36 and ER-alpha66 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-alpha36 mRNA levels than matched normal tissues regardless of their ER-alpha66 expression status. Down-regulation of ER-alpha36 mRNA was correlated with local progression, lymph node metastasis, and advanced cancer stage. The level of ER-alpha66 mRNA was lower in ER-alpha negative breast cancers compared with matched normal tissues. No differences in ER-alpha66 mRNA levels were observed during cancer progression. CONCLUSION: Down-regulation of ER-alpha36 is associated with carcinogenesis and progression of breast cancer.