Reproduction Abstracts

One of our major goals is to identify therapeutics and translate our finding to the clinical setting. Over the past few years, we have been focusing on two epithelial specific genes, CDH1 and WNT7A. CDH1 is a transmembrane glycoprotein, belonging to the cadherin superfamily of cell adhesion molecules. When we conditionally delete Cdh1 in the mouse uterus, infertility results due to disorganized cellular structure of the epithelium and ablation of endometrial glands. However, loss of Cdh1 alone in the uterus does not predispose mice to tumor formation. Mice with conditional ablation of Cdh1 and Trp53 demonstrate architectural features characteristic of type II endometrial carcinomas. In recent studies, we also found that absence of CDH1 and TP53 in endometrial cells initiates chronic inflammation, promotes tumor microenvironment following the recruitment of macrophages, and leads to aggressive endometrial carcinomas. In a second line of investigation, we have revealed a role for the specific WNT ligand WNT7A in epithelial ovarian cancer growth and progression. Our recent studies showed that FGF1 is an oncogenic, direct downstream target of WNT7A/β-catenin signaling, and the WNT7A/β-catenin–FGF1 signaling pathway has potential as a therapeutic target in ovarian cancer. These studies have been supported by NIH/NICHD HD0588222, NIH/NCI CA179214, and ACS-IL 139038.