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.
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Authors | Tae Hoon Kim, Jinrong Wang, Kevin Y Lee, Heather L Franco, Russell R Broaddus, John P Lydon, Jae-Wook Jeong, Francesco J Demayo |
Journal | Journal of oncology
(J Oncol)
Vol. 2010
Pg. 139087
( 2010)
ISSN: 1687-8450 [Print] Egypt |
PMID | 19884980
(Publication Type: Journal Article)
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