The Synergistic Effect of ConditionalPtenLoss and OncogenicK-rasMutation on Endometrial Cancer Development Occurs via Decreased Progesterone Receptor Action

[摘要] 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 ofPTENandK-rashave been associated with this disease. To study the roles ofPtenandK-rasin endometrial cancer, we generatedPtenablation and oncogenicK-rasmutation 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 thePtenandK-rassignaling pathways during endometrial tumorigenesis.

[学科分类] 肿瘤学