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

Oncogene volume 28, pages 31–40 (2009)Cite this article

Abstract

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 PRCre mouse with the Ctnnb1f(ex3)/+ mouse or Ctnnb1f/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, PRcre/+Ctnnb1f(ex3)/+, resulted in endometrial glandular hyperplasia, whereas ablation of β-catenin, PRcre/+Ctnnb1f/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.

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Acknowledgements

We thank Jinghua Li and Bryan Ngo for technical assistance; Janet DeMayo, MS for manuscript preparation. This study was supported by the NICHD and, the NIH R01HD042311 and NIH U54HD0077495 (to FJD), NIH R01-CA77530 and the Susan G Komen Award BCTR0503763 (to JPL), NIH 1P50CA098258-01 (to RRB), NIH R01HD057873 and pilot grant from NIH 1P50CA098258-01 (to JWJ), and the NICHD U54HD28934 (to the University of Virginia Center for Research in Reproduction Ligand Assay and Analysis Core).

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Authors and Affiliations

  1. Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, TX, USA

    J-W Jeong, H L Franco, S Y Tsai, J P Lydon & F J DeMayo

  2. Department of Obstetrics and Gynecology, Infertility & Reproductive Endocrinology Center, MizMedi Hospital, Seoul, Korea

    H S Lee

  3. Department of Pathology, University of Texas M.D. Anderson Cancer Center, Houston, TX, USA

    R R Broaddus

  4. Department of Pharmacology, Graduate School of Medicine, Kyoto University, Yoshida-Konoé-cho, Sakyo, Kyoto, Japan

    M M Taketo

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Jeong, JW., Lee, H., Franco, H. et al. β-catenin mediates glandular formation and dysregulation of β-catenin induces hyperplasia formation in the murine uterus. Oncogene 28, 31–40 (2009). https://doi.org/10.1038/onc.2008.363

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