{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,18]],"date-time":"2025-10-18T10:03:06Z","timestamp":1760781786233},"reference-count":46,"publisher":"Wiley","issue":"15","license":[{"start":{"date-parts":[[2014,8,29]],"date-time":"2014-08-29T00:00:00Z","timestamp":1409270400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["The Prostate"],"published-print":{"date-parts":[[2014,11]]},"abstract":"<jats:sec><jats:title>BACKGROUND<\/jats:title><jats:p>Wnt\/\u03b2\u2010catenin signaling is important for prostate development and cancer in humans. Activation of this pathway in differentiated luminal cells of mice induces high\u2010grade prostate intraepithelial neoplasia (HGPIN). Though the cell of origin of prostate cancer has yet to be conclusively identified, a castration\u2010resistant Nkx3.1\u2010expressing cell (CARN) may act as a cell of origin for prostate cancer.<\/jats:p><\/jats:sec><jats:sec><jats:title>METHODS<\/jats:title><jats:p>To activate Wnt\/\u03b2\u2010catenin signaling in CARNs, we crossed mice carrying tamoxifen\u2010inducible Nkx3.1\u2010driven Cre to mice containing loxP sites in order to either conditionally knock out adenomatous polyposis coli (Apc) or constitutively activate \u03b2\u2010catenin directly. We then castrated and hormonally regenerated these mice to target the CARN population.<\/jats:p><\/jats:sec><jats:sec><jats:title>RESULTS<\/jats:title><jats:p>Loss of Apc in hormonally normal mice induced HGPIN; however, after one or more rounds of castration and hormonal regeneration, Apc\u2010null CARNs disappeared. Alternatively, when \u03b2\u2010catenin was constitutively activated under the same conditions, HGPIN was apparent.<\/jats:p><\/jats:sec><jats:sec><jats:title>CONCLUSION<\/jats:title><jats:p>Activation of Wnt\/\u03b2\u2010catenin signaling via Apc deletion is sufficient to produce HGPIN in hormonally normal mice. Loss of Apc may destabilize the CARN population under regeneration conditions. When \u03b2\u2010catenin is constitutively activated, HGPIN occurs in hormonally regenerated mice. A second genetic hit is likely required to cause progression to carcinoma and metastasis. <jats:italic>Prostate 74:1506\u20131520, 2014<\/jats:italic>. \u00a9 2014 Wiley Periodicals, Inc.<\/jats:p><\/jats:sec>","DOI":"10.1002\/pros.22868","type":"journal-article","created":{"date-parts":[[2014,8,29]],"date-time":"2014-08-29T18:12:02Z","timestamp":1409335922000},"page":"1506-1520","source":"Crossref","is-referenced-by-count":16,"title":["Activation of Wnt\/\u03b2\u2010catenin signaling in a subpopulation of murine prostate luminal epithelial cells induces high grade prostate intraepithelial neoplasia"],"prefix":"10.1002","volume":"74","author":[{"given":"Kenneth C.","family":"Valkenburg","sequence":"first","affiliation":[{"name":"Center for Skeletal Disease &amp; Tumor Metastasis Van Andel Research Institute Grand Rapids Michigan"}]},{"given":"Xiuping","family":"Yu","sequence":"additional","affiliation":[{"name":"Department of Urological Surgery Vanderbilt University Medical Center Nashville Tennessee"}]},{"given":"Angelo M.","family":"De Marzo","sequence":"additional","affiliation":[{"name":"Department of Pathology Johns Hopkins University School of Medicine Baltimore Maryland"}]},{"given":"Tyler J.","family":"Spiering","sequence":"additional","affiliation":[{"name":"Center for Skeletal Disease &amp; Tumor Metastasis Van Andel Research Institute Grand Rapids Michigan"},{"name":"Wayne State University School of Medicine Detroit Michigan"}]},{"given":"Robert J.","family":"Matusik","sequence":"additional","affiliation":[{"name":"Department of Urological Surgery Vanderbilt University Medical Center Nashville Tennessee"}]},{"given":"Bart O.","family":"Williams","sequence":"additional","affiliation":[{"name":"Center for Skeletal Disease &amp; Tumor Metastasis Van Andel Research Institute Grand Rapids Michigan"}]}],"member":"311","published-online":{"date-parts":[[2014,8,29]]},"reference":[{"key":"e_1_2_7_2_1","unstructured":"American Cancer Society Inc.Cancer Facts & Figures. 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