Bi-directional Regulation of Human Progesterone Receptors and the Mitogen Activated Protein Kinase Pathway in Breast Cancer Cell Models

摘要: Breast cancers (BCs) often have increased mitogen-activated protein kinase (MAPK) activity. This pathway influences BC cell growth in part by targeting steroid hormone receptors. Activation of p42 and p44 MAPKs increases progesterone receptor (PR) transcriptional activity the presence progestins, triggers their rapid down-regulation ubiquitin-proteasome pathway. In turn, progestins increase expression type 1 factor tyrosine kinases that feed into MAPK activation. Recently, been shown to activate p42/p44 module a PR-dependent manner, but independently function as transcription factors. Mechanisms bi-directional cross-talk between these two pathways are becoming well-documented. Herein, we provide an overview primary ways which occurs, using examples from our work with human PR model receptor; demonstrate regulation subcellular localization, synergy, cyclin D1 expression. Cross-talk PR-mediated signaling events is important means regulatory genes coordinately regulated, may contribute hormonally responsive normal breast tissue BC.