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The Synergistic Effect of Conditional Pten Loss and Oncogenic K-ras Mutation on Endometrial Cancer Development Occurs via Decreased Progesterone Receptor Action.

Abstract
Endometrial cancer is the most common gynecological cancer. Estrogen-dependent endometrioid carcinoma is the most common type of endometrial cancer, and alterations in the expression of PTEN and K-ras have been associated with this disease. To study the roles of Pten and K-ras in endometrial cancer, we generated Pten ablation and oncogenic K-ras mutation in progesterone receptor positive cells (PR(cre/+)Pten(f/f)K-ras(G12D)). Double mutant mice dramatically accelerated the development of endometrial cancer compared to a single mutation of either gene. Histological analysis showed that all of the 1-month old double mutant female mice developed endometrial cancer with myometrial invasion. The expression of PR was downregulated in double mutant mice compared to a single mutation of either gene which resulted in decreased suppression of estrogen signaling. Therefore, these results suggest a synergistic effect of dysregulation of the Pten and K-ras signaling pathways during endometrial tumorigenesis.
AuthorsTae Hoon Kim, Jinrong Wang, Kevin Y Lee, Heather L Franco, Russell R Broaddus, John P Lydon, Jae-Wook Jeong, Francesco J Demayo
JournalJournal of oncology (J Oncol) Vol. 2010 Pg. 139087 ( 2010) ISSN: 1687-8450 [Print] Egypt
PMID19884980 (Publication Type: Journal Article)

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