Human Progesterone A-Form as a Target for New Drug Discovery in Human Breast Cancer

摘要

The role of the estrogen receptor (ER) in breast cancer has been suggested both by its ability to stimulate cell proliferation as well as the observation that ER is expressed ir 60% of primary breast tumor biopsies but only in 6% of normal breast tissue. Drugs which interfere with ER activity such as the antiestrogen Tamoxifen have been only partially successful in the treatment of breast cancers emphasizing the need for new targets as well as new pharmacological agents against these targets. The observation that antiprogestins such as RU486 could function as antiestrogens suggested that the progesterone receptor (PR) could be a potential target in the treatment of breast cancers. The goal of this project was to elucidate the mechanism of hPR-A transdominant repression by characterizing potential hPR-A-interacting partners which are necessary for ER transcriptional activation. We anticipate that new pharmacological agents against these targets could be used to treat breast cancers which currently escape endocrine intervention.