期刊
ONCOGENE
卷 32, 期 29, 页码 3477-3482出版社
NATURE PUBLISHING GROUP
DOI: 10.1038/onc.2012.376
关键词
uterine gland; Wnt/beta-catenin; Foxa2; cyclin; endometrial hyperplasia
资金
- Ministry of Education, Culture, Sports, Science and Technology (MEXT), Japan [22132006]
- National Institutes Health [R01ES016597-01A1]
- Grants-in-Aid for Scientific Research [23659783, 22132005, 23249076, 24590235, 23570085] Funding Source: KAKEN
The Wnt/beta-catenin signaling is essential for various organogenesis and is often implicated during tumorigenesis. Dysregulated beta-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/beta-catenin signaling in the uterine epithelia and the mechanism leading to the formation of endometrial hyperplasia. We report that conditional ablation and activation of beta-catenin in the uterine epithelia lead to aberrant epithelial structures and endometrial hyperplasia formation, respectively. We demonstrate that beta-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 beta-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 beta-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 beta-catenin and Foxa2 are essential features during the formation of endometrial hyperplasia.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据