Inactivation of Apc in the mouse prostate causes prostate carcinoma

Katia J. Bruxvoort, Holli M. Charbonneau, Troy A. Giambernardi, James C. Goolsby, Chao Nan Qian, Cassandra R. Zylstra, Daniel R. Robinson, Pradip Roy-Burman, Aubie K. Shaw, Bree D. Buckner-Berghuis, Robert E. Sigler, James H. Resau, Ruth Sullivan, Wade Bushman, Bart O. Williams

Research output: Contribution to journalArticlepeer-review

78 Scopus citations

Abstract

Alterations of the Wnt/β-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/β-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 β-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 β-catenin associated with prostate carcinoma suggests a role for β-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.

Original languageEnglish (US)
Pages (from-to)2490-2496
Number of pages7
JournalCancer Research
Volume67
Issue number6
DOIs
StatePublished - Mar 15 2007

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