Ming Jiang
Last active: 7/6/2016

Activation of beta-Catenin in mouse prostate causes HGPIN and continuous prostate growth after castration.

Yu X, Wang Y, Jiang M, Bierie B, Roy-Burman P, Shen MM, Taketo MM, Wills M, Matusik RJ
Prostate. 2009 69 (3): 249-62

PMID: 18991257 · PMCID: PMC4437562 · DOI:10.1002/pros.20877

BACKGROUND - The role of Wnt/beta-Catenin signaling in embryogenesis and carcinogenesis has been extensively studied in organs such as colon, lung and pancreas, but little is known about Wnt/beta-Catenin signaling in the prostate. Although stabilizing mutations in APC and beta-Catenin are rare in primary prostate tumors, recent studies suggest that cytoplasmic/nuclear beta-Catenin is associated with advanced, metastatic, hormone-refractory prostate carcinoma.

METHODS - To better understand the role of beta-Catenin in prostatic development and carcinogenesis, we studied Wnt expression during prostate development and activated Wnt/beta-Catenin signaling in the developing and adult prostate.

RESULTS - Our results demonstrated that during prostate development Wnt ligands display a dynamic expression pattern. Activation of beta-Catenin during prostate development caused epithelial hyperplasia followed by prostatic intraepithelial neoplasia (PIN) in prostate. In the adult prostate, activation of beta-Catenin resulted in high grade PIN (HGPIN) and continuous prostatic growth after castration. As a result of activation of beta-Catenin, AR was first up-regulated with the emergence of epithelial hyperplasia, but was later down-regulated when HGPIN developed. Furthermore, activation of beta-Catenin induced Foxa2 re-expression in adult prostate which normally is only expressed in the embryonic budding stage during prostate development.

CONCLUSIONS - The results from this study strongly suggest that Wnt/beta-Catenin signaling is involved in the regulation of prostate development and confirm that constitutive activation of this pathway enables the mouse prostate to grow after castration.

MeSH Terms (23)

Age Factors Androgens Animals beta Catenin Female Gene Expression Regulation, Developmental Gene Expression Regulation, Neoplastic Hepatocyte Nuclear Factor 3-beta Homeodomain Proteins Integrases Male Mice Mice, Inbred C57BL Mice, Mutant Strains Mice, Nude Orchiectomy Pregnancy Prostate Prostatic Intraepithelial Neoplasia Prostatic Neoplasms Signal Transduction Transcription Factors Wnt Proteins

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