title: Inactivation of Apc in the mouse prostate causes prostate carcinoma.
abstract: Alterations of the Wnt/beta-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/beta-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 beta-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 beta-catenin associated with prostate carcinoma suggests a role for beta-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.
authors.affiliation: Laboratory of Cell Signaling and Carcinogenesis, Van Andel Research Institute, Grand Rapids, Michigan 49503-2518, USA.
authors.forename: Katia J
authors.initials: KJ
authors.lastname: Bruxvoort
authors.forename: Holli M
authors.initials: HM
authors.lastname: Charbonneau
authors.forename: Troy A
authors.initials: TA
authors.lastname: Giambernardi
authors.forename: James C
authors.initials: JC
authors.lastname: Goolsby
authors.forename: Chao-Nan
authors.initials: CN
authors.lastname: Qian
authors.forename: Cassandra R
authors.initials: CR
authors.lastname: Zylstra
authors.forename: Daniel R
authors.initials: DR
authors.lastname: Robinson
authors.forename: Pradip
authors.initials: P
authors.lastname: Roy-Burman
authors.forename: Aubie K
authors.initials: AK
authors.lastname: Shaw
authors.forename: Bree D
authors.initials: BD
authors.lastname: Buckner-Berghuis
authors.forename: Robert E
authors.initials: RE
authors.lastname: Sigler
authors.forename: James H
authors.initials: JH
authors.lastname: Resau
authors.forename: Ruth
authors.initials: R
authors.lastname: Sullivan
authors.forename: Wade
authors.initials: W
authors.lastname: Bushman
authors.forename: Bart O
authors.initials: BO
authors.lastname: Williams
mesh_terms: D000483:Alleles; D000728:Androgens / Q000172:deficiency / Q000378:metabolism; D000818:Animals; D002467:Cell Nucleus / Q000378:metabolism; D002471:Cell Transformation, Neoplastic / Q000235:genetics* / Q000378:metabolism; D005260:Female; D017353:Gene Deletion; D015972:Gene Expression Regulation, Neoplastic; D020868:Gene Silencing; D017491:Genes, APC; D007150:Immunohistochemistry; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009376:Neoplasms, Hormone-Dependent / Q000235:genetics / Q000378:metabolism; D009928:Organ Specificity; D011470:Prostatic Hyperplasia / Q000235:genetics / Q000378:metabolism; D011471:Prostatic Neoplasms / Q000235:genetics* / Q000378:metabolism; D051176:beta Catenin / Q000378:metabolism
chemical_list: D000728:Androgens; D051176:beta Catenin