Objective: The novel estrogen receptor-α (ER-α) variant ER-α36 is reported to be functional in the es-trogen signaling pathway and is related to tamoxifen resistance in breast cancer. However, ER-α36 tends to be a...Objective: The novel estrogen receptor-α (ER-α) variant ER-α36 is reported to be functional in the es-trogen 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.展开更多
基金Project supported by the National Basic Research Program (973) of China (No. 2009CB521704)the National Natural Science Foundation of China (No. 30772510)+2 种基金the Ministry of Health of China (No. WKJ2006-2-008)the Department of Science and Technology of Zhejiang Province (No. 2007C24011)the Natural Science Foundation of Zhejiang Province (No. R206060), China
文摘Objective: The novel estrogen receptor-α (ER-α) variant ER-α36 is reported to be functional in the es-trogen 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.
