Regulation of estrogen-responsive genes; role of estrogen-induced oxidative stress and DNA repair proteins in mammary carcinogenesis and breast cancer progression; mechanisms by which estrogen promotes neuroprotection
The estrogen receptor mediates the effects of estrogens and antiestrogens in target cells by binding of the receptor to specific DNA sequences present in target genes. This interaction of the estrogen receptor with DNA plays a critical role in development and maintenance of reproductive, cardiovascular, neural, and skeletal cells. Although the receptor-DNA interaction is of paramount importance in the regulation of estrogen-responsive genes, the mechanism by which this interaction leads to changes in gene expression is not well understood.
Using highly sensitive molecular techniques, we are studying the expression of endogenous, estrogen-responsive genes in human breast cancer cells to define how chromatin structure plays a role in estrogen- and antiestrogen- regulated gene transcription. Understanding the mechanisms by which estrogen agonists and antagonists modulate gene expression is particularly important in light of the fact that these compounds are widely used in hormone replacement therapy and in breast cancer treatment and prevention.
We are also interested in examining the effect of estrogen on expression of oxidative stress and DNA repair proteins in the brain using brain slice cultures, primary neurons, and whole animals. These studies will help to define mechanisms by which estrogen alters protein expression in the brain and helps to protect the brain from ischemic injury as occurs during stroke.
National Science Foundation, National Science Council of Taiwan, and the National Institutes of Health.
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