乳腺癌及配对正常组织中 ER-α及其新型变异体 ER-α36 的 mRNA 定量谱分析。
Quantitative profiles of the mRNAs of ER-alpha and its novel variant ER-alpha36 in breast cancers and matched normal tissues.
机构信息
Cancer Center, the First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou 310003, China.
出版信息
J Zhejiang Univ Sci B. 2010 Feb;11(2):144-50. doi: 10.1631/jzus.B0900266.
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.
目的
新型雌激素受体-α（ER-α）变体 ER-α36 被报道在雌激素信号通路中具有功能，并且与乳腺癌中的他莫昔芬耐药性有关。然而，在没有他莫昔芬治疗的患者中，ER-α36 往往是一个有利于生存的因素。为了研究这一矛盾背后的机制，我们测定了乳腺癌及配对正常组织中 ER-α36 和全长 ER-α（ER-α66）的转录谱之间的差异。
方法
我们使用实时定量聚合酶链反应（PCR）检测了 74 对乳腺癌及其配对正常组织中 ER-α36 和 ER-α66 的信使 RNA（mRNA）水平，并将结果与它们的临床病理特征相关联。
结果
无论 ER-α66 的表达状态如何，乳腺癌中 ER-α36 mRNA 的表达水平均低于配对的正常组织。ER-α36 mRNA 的下调与局部进展、淋巴结转移和晚期癌症分期相关。与配对的正常组织相比，ER-α 阴性乳腺癌中 ER-α66 mRNA 的水平较低。在癌症进展过程中，未观察到 ER-α66 mRNA 水平的差异。
结论
ER-α36 的下调与乳腺癌的发生和进展有关。
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