Abstract
Since estrogen plays an important role in the growth and progression of human breast cancer, understanding the whole picture of estrogen signaling is a very important goal towards clarifying the biology of this disease. So far, we have studied the molecular mechanisms of estrogen-dependent breast carcinogenesis, specifically from the viewpoints of estrogen receptor (ER) gene expression and functional modulation of ER in breast cancer. Recent several years, we are focusing the development of new tools such as estrogen-responsive microarray and ERE-GFP reporter cells, which enable to characterize the estrogen-responsive genes in breast cancer cells and estrogen signal-sensitivity in individual breast cancer. We first identified estrogen-responsive genes by the comprehensive expression profiling in ER-positive breast cancer cells, and produced a custom-made estrogen-responsive microarray of narrowed-down subset. Using this microarray, we studied several basic researches for estrogen signaling such as the effect of estrogen-antagonists and endocrine-disruptors on estrogen-responsive gene expression profile. In this study, we found that transcription factor EGR3 is the bona fide target gene for ERa and involved in the estrogen-signaling pathway in breast cancer cells. Furthermore, the expression of another new estrogen-responsive gene HDAC6 significantly correlated with survival of breast cancer patients. In vitro study revealed that the HDAC6 caused the deacetylation of a-tubulin in cytosol and induced cell motility in ER-positive breast cancer cells. [J Physiol Sci. 2006;56 Suppl:S13]
