| First Author | Valkenburg KC | Year | 2014 |
| Journal | Prostate | Volume | 74 |
| Issue | 15 | Pages | 1506-20 |
| PubMed ID | 25175604 | Mgi Jnum | J:314978 |
| Mgi Id | MGI:6829195 | Doi | 10.1002/pros.22868 |
| Citation | Valkenburg KC, et al. (2014) Activation of Wnt/beta-catenin signaling in a subpopulation of murine prostate luminal epithelial cells induces high grade prostate intraepithelial neoplasia. Prostate 74(15):1506-20 |
| abstractText | BACKGROUND: Wnt/beta-catenin signaling is important for prostate development and cancer in humans. Activation of this pathway in differentiated luminal cells of mice induces high-grade prostate intraepithelial neoplasia (HGPIN). Though the cell of origin of prostate cancer has yet to be conclusively identified, a castration-resistant Nkx3.1-expressing cell (CARN) may act as a cell of origin for prostate cancer. METHODS: To activate Wnt/beta-catenin signaling in CARNs, we crossed mice carrying tamoxifen-inducible Nkx3.1-driven Cre to mice containing loxP sites in order to either conditionally knock out adenomatous polyposis coli (Apc) or constitutively activate beta-catenin directly. We then castrated and hormonally regenerated these mice to target the CARN population. RESULTS: Loss of Apc in hormonally normal mice induced HGPIN; however, after one or more rounds of castration and hormonal regeneration, Apc-null CARNs disappeared. Alternatively, when beta-catenin was constitutively activated under the same conditions, HGPIN was apparent. CONCLUSION: Activation of Wnt/beta-catenin 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 beta-catenin is constitutively activated, HGPIN occurs in hormonally regenerated mice. A second genetic hit is likely required to cause progression to carcinoma and metastasis. |
