Progesterone receptors induce FOXO1-dependent senescence in ovarian cancer cells

Autor:	Peter A. Argenta, Steve E. Kalloger, C. Blake Gilks, Caroline H. Diep, Carol A. Lange, Nathan J. Charles
Rok vydání:	2013
Předmět:	Senescence medicine.drug_class Cell Biology Biology Cell cycle medicine.disease Downregulation and upregulation Estrogen Progesterone receptor medicine Cancer research Ovarian cancer Receptor Molecular Biology Cell aging Developmental Biology
Zdroj:	Cell Cycle. 12:1433-1449
ISSN:	1551-4005 1538-4101
DOI:	10.4161/cc.24550
Popis:	Loss of nuclear progesterone receptors (PR) and low circulating progesterone levels are associated with increased ovarian cancer (OC) risk. However, PR are abundantly expressed in a significant percentage of serous and endometrioid ovarian tumors; patients with PR+ tumors typically experience longer progression-free survival relative to those with PR-null tumors. The molecular mechanisms of these protective effects are poorly understood. To study PR action in OC in the absence of added estrogen (i.e., needed to induce robust PR expression), we created ES-2 OC cells stably expressing vector control or GFP-tagged PR-B (GFP-PR). Progestin (R5020) stimulation of ES-2 cells stably expressing GFP-PR induced cellular senescence characterized by altered cellular morphology, prolonged survival, senescence-associated β-galactosidase activity, G1 cell cycle arrest and upregulation of the cell cycle inhibitor, p21, as well as the Forkhead-box transcription factor, FOXO1; these results repeated in unmodified ER+/PR+ P...
Databáze:	OpenAIRE
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