Quantification of estrogen receptor α and β expression in sporadic breast cancer
Quantification of estrogen receptor α and β expression in sporadic breast cancer
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DOI：
10.1038/sj.onc.1204917
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发表时间：
2001-12-06
期刊：
影响因子：
8
通讯作者：
Lidereau, R
中科院分区：
文献类型：
--
作者：
Bièche, I;Parfait, B;Lidereau, R
最近克隆的第二个雌激素受体（ER），命名为ER β，促使重新评估ER在乳腺癌中的作用。我们已经开发并验证了一种实时RT-PCR检测方法，以定量ER α和ER β基因在mRNA水平上的表达，在一系列的131例单侧浸润性原发性乳腺癌患者。虽然ER β表达在肿瘤组织中表现出广泛的变化，但其范围（近三个数量级）小于ER α（近四个数量级），表明ER β比ER α受到更严格的控制。我们观察到ER α和ER β表达之间呈负相关。“ER α-阴性”肿瘤（含有非常低的ER α mRNA水平）与SBR组织病理学分级III、RB 1低表达和ERBB 2过表达相关，证实ER α阴性描绘低分化肿瘤。ER α mRNA的量（而不是ER β mRNA的量）随着年龄的增长而增加，因此在绝经后患者的肿瘤中更高。ER α的表达（而不是ER β的表达）也与孕激素受体（PR）和PS2的表达密切相关，这表明ER α对启动子中含有ERE（雌激素反应元件）的基因具有比ER β更强的转录活性。有趣的是，我们发现ER β（而不是ER α）和CCND 1的表达之间存在负相关性，CCND 1在其启动子中含有AP 1元件而不是ERE。总之，这些数据证实了ER α和ER β在乳腺癌中发挥不同的作用，部分是通过不同类型的DNA增强子介导各种基因的转录。PR和PS2似乎主要是ER α反应基因，而CCND 1可能主要是ER β反应基因。我们的研究结果还强调了需要一种可靠的方法，提供全范围的定量值，以确定ER α和ER β的状态在临床上。
The recent cloning of a second estrogen receptor (ER), designated ER beta, has prompted a reevaluation of the role of ERs in breast cancer. We have developed and validated a real-time RT - PCR assay to quantify ER alpha and ER beta gene expression at the mRNA level in a series of 131 patients with unilateral invasive primary breast cancer. Although ER beta expression showed wide variations in tumor tissues, its range (nearly three orders of magnitude) was smaller than that of ER alpha (nearly four orders of magnitude), suggesting that ER beta is more tightly controlled than ER alpha. We observed a negative correlation between ER alpha and ER beta expression. 'ER alpha -negative' tumors (containing very low ER alpha mRNA levels) were associated with SBR histopathological grade III, RB1 underexpression and ERBB2 overexpression, confirming that ER alpha negativity delineates poorly differentiated tumors. The amount of ER alpha mRNA (but not that of ER beta mRNA) increased with age and was consequently higher in postmenopausal patients' tumors. Expression of ER alpha (but not that of ER beta) also correlated strongly with progesterone receptor (PR) and PS2 expression, suggesting that ER alpha has stronger transcriptional activity than ER beta towards genes containing an ERE (estrogen response element) in their promoters. Interestingly, we found a negative correlation between the expression of ER beta (but not ER alpha) and CCND1, which contains an AP1 element but not an ERE in its promoter. Taken together, these data confirm that ER alpha and ER beta play different roles in breast cancer, partly by mediating the transcription of various genes via different types of DNA enhancer. PR and PS2 seem to be mainly ER alpha -responsive genes, whereas CCND1 may be mainly ER beta -responsive. Our findings also underline the need for a reliable method, providing full range of quantitative values, to determine ER alpha and ER beta status in the clinical setting.