The Synergistic Effect of Conditional Pten Loss and Oncogenic K-ras Mutation on Endometrial Cancer Development Occurs via Decreased Progesterone Receptor Action.
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.
Kim
Tae Hoon
TH
Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, TX 77030, USA.
Wang
Jinrong
J
Lee
Kevin Y
KY
Franco
Heather L
HL
Broaddus
Russell R
RR
Lydon
John P
JP
Jeong
Jae-Wook
JW
Demayo
Francesco J
FJ