Previously we reported caveolin-1 (Cav-1) overexpression in prostate cancer (PCa) cells and demonstrated that it promotes PCa progression.
Here, we report that Cav-1 was overexpressed in 41.7% (15 of 36) of high-grade prostatic intraepithelial neoplasia (HGPIN) specimens obtained during radical prostatectomies. Positive correlations exist between Cav-1-positive (Cav-1+) HGPIN and Cav-1+ primary PCa (rho = 0.655, P< 0.0001) and between Cav-1 and c-Myc expression in HGPIN (rho = 0.41, P = 0.032). To determine whether Cav-1 cooperates with c-Myc in development of premalignant lesions and PCa in vivo, we generated transgenic mice with c-Myc overexpression driven by the ARR2PB promoter. In this ARR2PB-c-myc model, Cav-1 overexpression was found in mouse PIN (mPIN) lesions and PCa cells and was associated with a significantly higher ratio of proliferative to apoptotic labeling in mPIN lesions than in the Cav-1-negative epithelia adjacent to those lesions (10.02 vs 4.34; P = 0.007). Cav-1 overexpression was also associated with increased levels of P-Akt and VEGF-A, which were previously associated with Cav-1-induced PCa cell survival and positive-feedback regulation of cellular Cav-1 levels, respectively. In multiple PCa cell lines, Cav-1 protein (but not mRNA) was induced by c-Myc transfection, whereas VEGF siRNA transfection abrogated c-Myc-induced Cav-1 overexpression, suggesting a c-Myc-VEGF-Cav-1 signaling axis. Overall, our results suggest that Cav-1 is associated with c-Myc in the development of HGPIN and PCa. Further, Cav-1 overexpression in HGPIN is potentially a biomarker for early identification of patients who tend to develop Cav-1+ primary PCa.
Written by:
Yang G, Goltsov AA, Ren C, Kurosaka S, Edamura K, Logothetis R, Demayo FJ, Troncoso P, Blando J, Digiovanni J, Thompson TC. Are you the author?
UT M. D. Anderson Center.
Reference: Mol Cancer Res. 2011 Dec 5. [Epub ahead of print]
PubMed Abstract
PMID: 22144662
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