During FY1999 we built upon key observations that we made concerning the mechanisms by which steroid receptors activate transcription within breast cancer cells. We demonstrated that proteins involved in the manipulation of chromatin structure, so called chromatin remodeling machines, represent the key components in the cascade of events that results in the activation of the genetic program in human breast cancer cells. We have analyzed the activity of the glucocorticoid and progesterone receptors within breast cancer cells modified to over express components of the chromatin remodeling machines. These cells display an altered response to a variety of clinically important hormone antagonist and will be useful in evaluating various anti- hormone strategies in breast cancer. In addition they are a unique resource to evaluate and characterize the impact of a number of environmental agents in human cells. To this end we have continued to develop methodologies that allow us to look a protein-DNA interactions within living cells, so called in vivo footprinting, as well as changes at the control regions of specific genes within living cell, chromatin immunoprecipitation (CHIP) assays. - Glucocorticoids, Progesterone, Synthetic Glucocorticoids, Synthetic Progestins, Anti-glucocorticoids, Anti-progestins Breast Cancer
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