title: 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.
authors.affiliation: Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, TX 77030, USA.
authors.forename: Tae Hoon
authors.initials: TH
authors.lastname: Kim
authors.forename: Jinrong
authors.initials: J
authors.lastname: Wang
authors.forename: Kevin Y
authors.initials: KY
authors.lastname: Lee
authors.forename: Heather L
authors.initials: HL
authors.lastname: Franco
authors.forename: Russell R
authors.initials: RR
authors.lastname: Broaddus
authors.forename: John P
authors.initials: JP
authors.lastname: Lydon
authors.forename: Jae-Wook
authors.initials: JW
authors.lastname: Jeong
authors.forename: Francesco J
authors.initials: FJ
authors.lastname: Demayo