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Activation of β‐Catenin in mouse prostate causes HGPIN and continuous prostate growth after castration
Author(s) -
Yu Xiuping,
Wang Yongqing,
Jiang Ming,
Bierie Brian,
RoyBurman Pradip,
Shen Michael M.,
Taketo Makoto Mark,
Wills Marcia,
Matusik Robert J.
Publication year - 2008
Publication title -
the prostate
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.295
H-Index - 123
eISSN - 1097-0045
pISSN - 0270-4137
DOI - 10.1002/pros.20877
Subject(s) - prostate , wnt signaling pathway , hyperplasia , beta catenin , cancer research , prostate cancer , medicine , biology , signal transduction , cancer , microbiology and biotechnology
Abstract BACKGROUND The role of Wnt/β‐Catenin signaling in embryogenesis and carcinogenesis has been extensively studied in organs such as colon, lung and pancreas, but little is known about Wnt/β‐Catenin signaling in the prostate. Although stabilizing mutations in APC and β‐Catenin are rare in primary prostate tumors, recent studies suggest that cytoplasmic/nuclear β‐Catenin is associated with advanced, metastatic, hormone‐refractory prostate carcinoma. METHODS To better understand the role of β‐Catenin in prostatic development and carcinogenesis, we studied Wnt expression during prostate development and activated Wnt/β‐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 β‐Catenin during prostate development caused epithelial hyperplasia followed by prostatic intraepithelial neoplasia (PIN) in prostate. In the adult prostate, activation of β‐Catenin resulted in high grade PIN (HGPIN) and continuous prostatic growth after castration. As a result of activation of β‐Catenin, AR was first up‐regulated with the emergence of epithelial hyperplasia, but was later down‐regulated when HGPIN developed. Furthermore, activation of β‐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/β‐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. Prostate 69:249–262, 2009. © 2008 Wiley‐Liss, Inc.