IBYME   02675
INSTITUTO DE BIOLOGIA Y MEDICINA EXPERIMENTAL
Unidad Ejecutora - UE
congresos y reuniones científicas
Título:
Kinases and steroid receptors: new relationships for old players.
Autor/es:
SARAGÜETA, PATRICIA
Lugar:
Buenos Aires
Reunión:
Workshop; ?Steroid Hormones in Physiology and Disease: from Bench toBedside?; 2012
Institución organizadora:
SAIC
Resumen:
Progesterone controls proliferation of rat endometrial stromal cells during the periimplantation phase of pregnancy. We describe that picomolar concentration of progestin R5020 mimics this control in UIII endometrial stromal cells via Erk1-2 and/or Akt activation mediated by PR-ER interaction, independently of its transcriptional activity. We identify novel primary downstream targets of this pathway in UIII cells and their possible role in physiological decidual proliferation. Our results show, for the first time, a set of novel primary downstream targets of a cytoplasmic pathway of PR signaling. The data indicate that progestin-dependent proliferation in stromal endometrial cells could be due in part to the action of immediate early-regulated transcription factors targeting cell cycle regulatory molecules and the inhibition of repressors of transcription and cell cycle. Microarray analysis of global gene expression changes in UIII cells treated for 45 min with progestin identified 97 up- and 341 down-regulated genes. Particularly, R5020 regulates Ccnd1, JunD, Usf1, Gfi1, Cyr61, and Cdkn1b through PR activation of ligand-free ER, ERK1-2 or AKT. The induction of the transcription factor USF1 and its target CDC2 were validated at the protein level and Cdc2 knockdown blocked R5020 induced cell proliferation. In 8 days pregnant rats CDC2 increased in antimesometrial decidua in association with activated ERK1-2 and PR. We conclude that progestin induced proliferation of endometrial stromal cells requires ERK1-2 mediated regulation of early transcription factors targeting the cell cycle gene Cdc2.