IBYME   02675
INSTITUTO DE BIOLOGIA Y MEDICINA EXPERIMENTAL
Unidad Ejecutora - UE
congresos y reuniones científicas
Título:
The transcription factor USF1 and its target gene Cdc2 mediate progestin-dependent proliferation of endometrial stromal cells.
Autor/es:
VALLEJO, GRISELDA; LA GRECA, ALEJANDRO; BEATO, MIGUEL; SARAGÜETA, PATRICIA
Reunión:
Simposio; Frontiers in Reproduction XVII Annual Symposium; 2014
Resumen:
Although non-genomic steroid receptor pathways have been widely studied, little is known about the direct gene expression changes that take place as a consequence of their activation. Progesterone controls proliferation of rat endometrial stromal cells during the peri-implantation phase of pregnancy. We showed that picomolar concentration of progestin R5020 mimics this control in UIII endometrial stromal cells via ERK1-2 and AKT activation mediated by interaction of Progesterone Receptor (PR) with Estrogen Receptor beta (ERb) and without transcriptional activity of endogenous PR and ER. The most over-represented molecular functions identified by microarrays analysis were transcription factors and regulatory factors associated with cell proliferation and cell cycle. Here we verified that progestins regulate Usf1 transcription factor, and its target Cdc2 through PR-mediated activation in the absence of genomic PR binding. ChIP experiments show that progestin promoted the interaction of USF1 with the proximal promoter of the Cdc2 gene. Usf1 knockdown abolished Cdc2 progestin-dependent transcriptional regulation and cell proliferation, which is also blocked by Cdc2 knockdown. We conclude that progestin-induced proliferation of endometrial stromal cells is mediated by ERK1-2 and AKT dependent early regulation of USF1, which directly induces Cdc2. To our knowledge, this is the first description of an early target gene of progestin-activated classical PR via crosstalk with protein kinases and independently of hormone receptor binding to the genomic targets in endometrium.