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Journal of Oncology
Volume 2010, Article ID 139087, 9 pages
Research Article

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

1Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, TX 77030, USA
2Joslin Diabetes Center, Harvard Medical School, Boston, MA 02215, USA
3Department of Pathology, University of Texas, M.D. Anderson Cancer Center, Houston, TX 77030, USA

Received 27 May 2009; Accepted 10 August 2009

Academic Editor: Gudrun Pohl

Copyright © 2010 Tae Hoon Kim et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.


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 . 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.