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PC-1/PrLZ Contributes to Malignant Progression in Prostate Cancer

¹ Laboratory of Molecular Oncology and ² Protein Engineering Laboratory, Institute of Biotechnology, Beijing, P. R. China; and ³ Molecular Urology and Therapeutics, Department of Urology, Emory University School of Medicine, Atlanta, Georgia

Requests for reprints: Jian-guang Zhou, Institute of Biotechnology, 27 Taiping Road, Haidian District, Beijing 100850, P.R. China. Phone: 86-10-66931807; Fax: 86-10-68248045; E-mail: zhou.jianguang{at}yahoo.com.cn.

PC-1/PrLZ gene overexpression has been identified to be associated with prostate cancer progression. Previous studies have revealed that PC-1 possesses transforming activity and confers malignant phenotypes to mouse NIH3T3 cells. However, the functional relevance of PC-1 expression changes during prostate cancer development and progression remains to be evaluated. In this study, gain-of-function and loss-of-function analyses in LNCaP and C4-2 cells, respectively, were implemented. Experimental data showed that PC-1 expression was in positive correlation with prostate cancer cell growth and anchor-independent colony formation in vitro, as well as tumorigenicity in athymic BALB/c mice. Moreover, PC-1 expression was also found to promote androgen-independent progression and androgen antagonist Casodex resistance in prostate cancer cells. These results indicate that PC-1 contributes to androgen-independent progression and malignant phenotypes in prostate cancer cells. Furthermore, molecular evidence revealed that PC-1 expression stimulated Akt/protein kinase B signaling pathway, which has been implicated to play important roles in promoting androgen refractory progression in prostate cancer. Increased PC-1 levels in C4-2 cells may represent an adaptive response in prostate cancer, mediating androgen-independent growth and malignant progression. Inhibiting PC-1 expression may represent a novel therapeutic strategy to delay prostate cancer progression. [Cancer Res 2007;67(18):8906–13]