beta-catenin mediates glandular formation and dysregulation of beta-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. 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.
Jeong
J-W
JW
Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, TX 77030, USA.
Lee
H S
HS
Franco
H L
HL
Broaddus
R R
RR
Taketo
M M
MM
Tsai
S Y
SY
Lydon
J P
JP
DeMayo
F J
FJ
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*
C495267:CTNNB1 protein, mouse; D051176:beta Catenin