Cell Cycle Dependent Regulation of Human Progesterone Receptor in Breast Cancer
Annual summary rept. 19 Apr 2002-18 Sep 2004
MINNESOTA UNIV MINNEAPOLIS
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Steroid hormones are required for normal breast development and play a key role in breast cancer. The steroid hormone progesterone regulates cell growth in the normal mammary gland and uterus by cell cycle phase-specific actions. Breast cancers are often characterized by increased growth factor signaling pathways and numerous cell cycle alterations, including decreased levels of p27 and increased levels of cyclins D1, D2 and E. Progestins, via the activation of progesterone receptor PR, activate cyclin dependent kinase 2 CDK2 and raise levels of cyclins D and E PR are phosphorylated by CDK2 in vitro and in vivo at multiple sites including serine 400 Ser400. In addition, breast cancer cell growth is controlled, in part by, cross-talk between steroid hormone and growth factor signaling pathways. The purpose of these studies is to investigate the role that growth factors and cell cycle molecules play on the regulation of PR by phosphorylation of Ser400.
- Medicine and Medical Research