title: beta-catenin mediates glandular formation and dysregulation of beta-catenin induces hyperplasia formation in the murine uterus.
abstract: Endometrioid adenocarcinoma is the most frequent form of endometrial cancer, usually developing in pre- and peri-menopausal women. beta-catenin abnormalities are common in endometrioid type endometrial carcinomas with squamous differentiation. To investigate the role of beta-catenin (Ctnnb1) in uterine development and tumorigenesis, mice were generated which expressed a dominant stabilized beta-catenin or had beta-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 beta-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 beta-catenin, PR(cre/+)Ctnnb1(f(ex3)/+), resulted in endometrial glandular hyperplasia, whereas ablation of beta-catenin, PR(cre/+)Ctnnb1(f/f), induced squamous cell metaplasia in the murine uterus. Therefore, we have demonstrated that correct regulation of beta-catenin is important for uterine function as well as in the regulation of endometrial epithelial differentiation.
authors.affiliation: Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, TX 77030, USA.
authors.forename: J-W
authors.initials: JW
authors.lastname: Jeong
authors.forename: H S
authors.initials: HS
authors.lastname: Lee
authors.forename: H L
authors.initials: HL
authors.lastname: Franco
authors.forename: R R
authors.initials: RR
authors.lastname: Broaddus
authors.forename: M M
authors.initials: MM
authors.lastname: Taketo
authors.forename: S Y
authors.initials: SY
authors.lastname: Tsai
authors.forename: J P
authors.initials: JP
authors.lastname: Lydon
authors.forename: F J
authors.initials: FJ
authors.lastname: DeMayo
mesh_terms: D000818:Animals; D002454:Cell Differentiation / Q000235:genetics; D049109:Cell Proliferation; D002471:Cell Transformation, Neoplastic / Q000235:genetics* / Q000473:pathology; D004195:Disease Models, Animal; D004714:Endometrial Hyperplasia / Q000235:genetics* / Q000473:pathology; D004717:Endometrium / Q000254:growth & development* / Q000473:pathology; D005260:Female; D007247:Infertility, Female / Q000235:genetics; D051379:Mice; D008817:Mice, Mutant Strains; D051176:beta Catenin / Q000235:genetics / Q000502:physiology*
chemical_list: C495267:CTNNB1 protein, mouse; D051176:beta Catenin