This Article Full Text Full Text (PDF) Supplementary Data Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Bruxvoort, K. J. Articles by Williams, B. O. Search for Related Content PubMed PubMed Citation Articles by Bruxvoort, K. J. Articles by Williams, B. O.

Inactivation of Apc in the Mouse Prostate Causes Prostate Carcinoma

¹ Laboratory of Cell Signaling and Carcinogenesis, ² Laboratory of Analytical, Cellular, and Molecular Microscopy, and ³ Laboratory of Cancer Genetics, Van Andel Research Institute, Grand Rapids, Michigan; ⁴ University of Southern California, Los Angeles, California; ⁵ Division of Urology and McArdle Laboratory for Cancer Research; and ⁶ University of Wisconsin Comprehensive Cancer Center, University of Wisconsin, Madison, Wisconsin

Requests for reprints: Bart O. Williams, Laboratory of Cell Signaling and Carcinogenesis, Van Andel Research Institute, 333 Bostwick Avenue Northeast, Grand Rapids, MI 49503-2518. Phone: 616-234-5308; Fax: 616-234-5309; E-mail: Bart.Williams{at}vai.org.

Alterations of the Wnt/ß-catenin signaling pathway are positively associated with the development and progression of human cancer, including carcinoma of the prostate. To determine the role of activated Wnt/ß-catenin signaling in mouse prostate carcinogenesis, we created a mouse prostate tumor model using probasin-Cre–mediated deletion of Apc. Prostate tumors induced by the deletion of Apc have elevated levels of ß-catenin protein and are highly proliferative. Tumor formation is fully penetrant and follows a consistent pattern of progression. Hyperplasia is observed as early as 4.5 weeks of age, and adenocarcinoma is observed by 7 months. Continued tumor growth usually necessitated sacrifice between 12 and 15 months of age. Despite the high proliferation rate, we have not observed metastasis of these tumors to the lymph nodes or other organs. Surgical castration of 6-week-old mice inhibited tumor formation, and castration of mice with more advanced tumors resulted in the partial regression of specific prostate glands. However, significant areas of carcinoma remained 2 months postcastration, suggesting that tumors induced by Apc loss of function are capable of growth under conditions of androgen depletion. We conclude that the prostate-specific deletion of Apc and the increased expression of ß-catenin associated with prostate carcinoma suggests a role for ß-catenin in prostate cancer and offers an appropriate animal model to investigate the interaction of Wnt signaling with other genetic and epigenetic signals in prostate carcinogenesis. [Cancer Res 2007;67(6):2490–6]

This article has been cited by other articles:

				P. G. Febbo Epigenetic Events Highlight the Challenge of Validating Prognostic Biomarkers During the Clinical and Biologic Evolution of Prostate Cancer J. Clin. Oncol., July 1, 2009; 27(19): 3088 - 3090. [Full Text] [PDF]

				H. B. Pearson, T. J. Phesse, and A. R. Clarke K-ras and Wnt Signaling Synergize to Accelerate Prostate Tumorigenesis in the Mouse Cancer Res., January 1, 2009; 69(1): 94 - 101. [Abstract] [Full Text] [PDF]

				H. B. Pearson, A. McCarthy, C. M.P. Collins, A. Ashworth, and A. R. Clarke Lkb1 Deficiency Causes Prostate Neoplasia in the Mouse Cancer Res., April 1, 2008; 68(7): 2223 - 2232. [Abstract] [Full Text] [PDF]

				M. Mimeault, P. P. Mehta, R. Hauke, and S. K. Batra Functions of Normal and Malignant Prostatic Stem/Progenitor Cells in Tissue Regeneration and Cancer Progression and Novel Targeting Therapies Endocr. Rev., April 1, 2008; 29(2): 234 - 252. [Abstract] [Full Text] [PDF]