β-catenin mediates glandular formation and dysregulation of β-catenin induces hyperplasia formation in the murine uterus

Endometrioid adenocarcinoma is the most frequent form of endometrial cancer, usually developing in pre- and peri-menopausal women. β-catenin abnormalities are common in endometrioid type endometrial carcinomas with squamous differentiation. To investigate the role of β-catenin (Ctnnb1) in uterine development and tumorigenesis, mice were generated which expressed a dominant stabilized β-catenin or had β-catenin conditionally ablated in the uterus by crossing the PR^Cre mouse with the Ctnnb1 ^f(ex3)/+ mouse or Ctnnb1^f/f mouse, respectively. Both of the β-catenin mutant mice have fertility defects and the ability of the uterus to undergo a hormonally induced decidual reaction was lost. Expression of the dominant stabilized β-catenin, PR^cre/+Ctnnb1 ^f(ex3)/+, resulted in endometrial glandular hyperplasia, whereas ablation of β-catenin, PR^cre/+Ctnnb1^f/f, induced squamous cell metaplasia in the murine uterus. Therefore, we have demonstrated that correct regulation of β-catenin is important for uterine function as well as in the regulation of endometrial epithelial differentiation.