Abstract 2289: A novel mouse model of endometrial cancer: epithelial specific Pten deletion with lactoferrin-iCre

Abstract

Abstract Endometrial cancer is a common gynecological malignancy, causing approximately 8,000 deaths each year in the United States. Underlying causes of endometrial cancer are not clearly understood, and treatment options for patients with advanced stages are limited. Animal models that spontaneously develop cancer are powerful tools for studying the mechanism of cancer initiation and progression and for developing treatment strategies. We previously created a mouse model of endometrial cancer in which the floxed phosphatase and tensin homologue (Pten) gene was deleted by Cre expression under the control of a progesterone receptor (PR) promoter. Pten is a tumor suppressor with the highest frequency of mutation in human endometrial cancer. In the PtenloxP/loxP/PR-Cre mouse model, uterine deletion of Pten resulted in complex atypical hyperplasia of the uterine epithelium by three weeks of age with cancer occurring by one month. As PR is expressed in the epithelium, stroma, and myometrium compartments, the question remains whether Pten deletion in the uterine epithelium alone contributes to endometrial cancer since human endometrial cancer is derived from epithelial cells. To address this question, we used lactoferrin-iCre (Ltf-Cre) mice to specifically delete Pten in the uterine epithelium, since lactoferrin is restricted to the epithelium of adult mice. We found that PtenloxP/loxP/Ltf-Cre mice develop complex atypical hyperplasia in uterine epithelium by three months of age, whereas uteri from immature mice are normal. These results demonstrate that Pten deletion specifically in the uterine epithelium can contribute to toward endometrial cancer in mice. This mouse model will help us to study in detail the initiation and progression of endometrial cancer. This study was supported in parts by grants from NIH-P01-CA-77839 (S. K. D). Citation Format: Takiko Daikoku, Jumpei Terakawa, Sudhansu K. Dey. A novel mouse model of endometrial cancer: epithelial specific Pten deletion with lactoferrin-iCre. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 2289. doi:10.1158/1538-7445.AM2015-2289