Expression and functional regulation of estrogen receptor in hormone-dependent cancer

雌激素及其受体在乳腺癌的发生、发展中起重要作用。尤其是ERα不仅与乳腺癌的临床预后密切相关，而且是内分泌治疗的重要靶点。我们从雌激素受体表达和功能的肿瘤特异性现象方面，对乳腺癌发生发展的分子机制进行了研究。最近，我们制作了一个定制的cDNA微阵列，用于分析雌激素反应基因的表达谱，并将其应用于一些基础和临床研究，如了解乳腺癌细胞中的雌激素信号通路和预测原发性乳腺癌患者对内分泌治疗的个体反应。在本研究中，我们发现了几个新的雌激素受体靶基因，并揭示了其中一些可能影响乳腺癌患者的临床结局。该基因芯片还可用于分析ERβ等细胞内因子对ERα的功能调控。此外，我们正在开发一种新的工具，用于使用ERE-GFP指示细胞分析新型芳香酶抑制剂对个体乳腺癌患者的影响。我们希望这些方法可以通过评估个体对内分泌治疗的反应来为患者提供临床益处。

Estrogen and its receptor play important roles in genesis and malignant progression of breast cancer. In particular, ERα is not only closely associated with clinical outcome of breast cancer but also most important target of endocrine therapy. We have been studied the molecular mechanisms of carcinogenesis and development of human breast cancer so far, in terms of cancer-specific phenomenon of expression and function of estrogen receptor. Recently, we have produced a custom-made cDNA microarray for analyzing estrogen-responsive gene expression profile, and applied it to several basic and clinical studies, such as understanding the estrogen signaling pathway in breast cancer cells and prediction of individual response to endocrine therapy among primary breast cancer patients. In this study, we found several novel target genes for estrogen receptor, and revealed that some of them might impact to clinical outcome of breast cancer patients. This microarray was also useful to analyze the functional modulation of ERα controlled by the intracellular factors such as ERβ. Furthermore, we are developing a new tool for analyzing the effect of new aromatase inhibitors on individual breast cancer patients using ERE-GFP-indicator cells. We hope that these approaches could provide clinical benefits to patients by assessment of individual response to endocrine therapy.