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

• Main Authors: Tae Hoon Kim, Jinrong Wang, Kevin Y. Lee, Heather L. Franco, Russell R. Broaddus, John P. Lydon, Jae-Wook Jeong, Francesco J. DeMayo
• Format: Article
• Language: English
• Published: Hindawi Limited 2010-01-01
• Series: Journal of Oncology
• Online Access: http://dx.doi.org/10.1155/2010/139087

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 (PRcre/+Ptenf/fK-rasG12D). 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.