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

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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.