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

Abstract EN

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.