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

激素依赖性癌症中雌激素受体的表达和功能调节

基本信息

批准号：
14571170
负责人：
HAYASHI Shin-ichi
金额：
$ 2.11万
依托单位：
Saitama Cancer Center
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
2002
资助国家：
日本
起止时间：
2002 至 2003
项目状态：
已结题

项目摘要

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.

雌激素及其受体在乳腺癌的发生和恶性发展中起重要作用。特别是，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。迄今为止，我们从雌激素受体的肿瘤特异性表达和功能等方面研究了人类乳腺癌发生发展的分子机制。最近，我们制作了一个定制的cDNA微阵列，用于分析雌激素应答基因表达谱，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，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，并揭示了其中一些基因可能影响乳腺癌患者的临床预后。该芯片还可用于分析细胞内因子如ERβ控制的ERα的功能调节。此外，我们正在开发一种新的工具，用于分析新的芳香酶抑制剂对个体乳腺癌患者的影响，使用ere - gfp指示细胞。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。