title: β-Catenin signaling regulates Foxa2 expression during endometrial hyperplasia formation.
abstract: The Wnt/β-catenin signaling is essential for various organogenesis and is often implicated during tumorigenesis. Dysregulated β-catenin signaling is associated with the formation of endometrial adenocarcinomas (EACs), which is considered as the common form of endometrial cancer in women. In the current study, we investigate the downstream target of Wnt/β-catenin signaling in the uterine epithelia and the mechanism leading to the formation of endometrial hyperplasia. We report that conditional ablation and activation of β-catenin in the uterine epithelia lead to aberrant epithelial structures and endometrial hyperplasia formation, respectively. We demonstrate that β-catenin regulates Foxa2 with its candidate upstream region for the uterine epithelia. Furthermore, knockdown of Foxa2 leads to defects in cell cycle regulation, suggesting a possible function of Foxa2 in the control of cell proliferation. We also observe that β-catenin and Foxa2 expression levels are augmented in the human specimens of complex atypical endometrial hyperplasia, which is considered to have a greater risk of progression to EACs. Thus, our study indicates that β-catenin regulates Foxa2 expression, and this interaction is possibly essential to control cell cycle progression during endometrial hyperplasia formation. Altogether, the augmented expression levels of β-catenin and Foxa2 are essential features during the formation of endometrial hyperplasia.
authors.affiliation: Department of Developmental Genetics, Institute of Advanced Medicine, Wakayama Medical University, Wakayama, Kansai, Japan.
authors.forename: M
authors.initials: M
authors.lastname: Villacorte
authors.forename: K
authors.initials: K
authors.lastname: Suzuki
authors.forename: A
authors.initials: A
authors.lastname: Hirasawa
authors.forename: Y
authors.initials: Y
authors.lastname: Ohkawa
authors.forename: M
authors.initials: M
authors.lastname: Suyama
authors.forename: T
authors.initials: T
authors.lastname: Maruyama
authors.forename: D
authors.initials: D
authors.lastname: Aoki
authors.forename: Y
authors.initials: Y
authors.lastname: Ogino
authors.forename: S
authors.initials: S
authors.lastname: Miyagawa
authors.forename: T
authors.initials: T
authors.lastname: Terabayashi
authors.forename: Y
authors.initials: Y
authors.lastname: Tomooka
authors.forename: N
authors.initials: N
authors.lastname: Nakagata
authors.forename: G
authors.initials: G
authors.lastname: Yamada
mesh_terms: D000818:Animals; D004714:Endometrial Hyperplasia / Q000378:metabolism*; D005260:Female; D005786:Gene Expression Regulation; D055785:Gene Knockdown Techniques; D051542:Hepatocyte Nuclear Factor 3-beta / Q000096:biosynthesis*; D006801:Humans; D007150:Immunohistochemistry; D051379:Mice; D020411:Oligonucleotide Array Sequence Analysis; D015398:Signal Transduction / Q000502:physiology*; D051176:beta Catenin / Q000378:metabolism*
chemical_list: C496502:FOXA2 protein, human; C496503:Foxa2 protein, mouse; D051176:beta Catenin; D051542:Hepatocyte Nuclear Factor 3-beta