A common docking (CD) domain in progesterone receptor-B links rapid signaling events to STAT5-dependent gene expression required for breast cancer cell proliferation.

摘要: Progesterone receptors (PR) are critical context-dependent transcription factors required for normal uterine (PR-A) and mammary gland (PR-B) development. Progesterone is proliferative in the breast, where PR target genes include paracrine factors that mediate mammary stem cell self-renewal. In the context of altered signal transduction that typifies breast tumorigenesis, dysregulated (i.e. hyper-phosphorylated) PRs likely contribute to tumor progression by promoting cancer cell pro-survival and proliferation. Notably, in breast cancer cells, progestin-bound PRs induce rapid MAPK activation leading to selective regulation of growth-promoting genes by phosphorylated PR species. Functional domains within PR that interact with c-Src and estrogen receptors (ER) have been identified as indirect routes to MAPK activation. Herein, we describe a common docking (CD) domain located within the PR-B N-terminus, a …