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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    G 12 D  ). 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.

journal of oncology

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

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