Abstract 3922: Lef-1 is differentially expressed in endometrial cancer and appears to target cyclin D1 in endometrial tissue

Abstract

Abstract Objectives: The molecular pathways involving endometrial carcinogenesis and gland formation are currently unclear. We have previously reported on the involvement of Lymphoid Enhancing Factor-1 (Lef-1), a transcription factor, in the development and maintenance of glands within the mouse uterus. We have also demonstrated the overexpression of Lef-1 within human cancer samples. Cyclin D1, a downstream target of Lef-1, has been shown to be over-expressed in a myriad of human cancers. We hypothesize that Lef-1 is differentially expressed in human endometrial cancers and that cyclin D1 is regulated by Lef-1 in gland formation and cancer. Methods: Using Lef-1 knock out (KO) mice and wild type (WT) controls we characterized the expression of cyclin D1 within the endometrial glands of the developing mouse endometrium. Using Western blot analysis and real time PCR, we also characterized and identified Lef-1 expression in different human endometrial cancer samples. Using both normal and cancerous human endometrial tissue samples, we immunostained for Lef-1 and cyclin D1 protein. Results: Lef-1 expression is increased in certain subtypes of human endometrial cancer. In WT mice, cyclin D1 is localized to the developing gland bud by day 7, as compared to the KO mice, which express no cyclin D1 during this day. There appears to be cyclin D1 immunostaining within the same Lef-1 expressing cells within human endometrial cancers. Conclusions: Lef-1 is overexpressed in specific subtypes of human endometrial cancer. Cyclin D1 appears to be present during endometrial gland formation within the mouse uterus and present within certain human endometrial cancer cells that express Lef-1. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 3922.