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Transcriptional Silencing of Zinc Finger Protein 185 Identified by Expression Profiling Is Associated with Prostate Cancer Progression¹

Department of Urology [D. K. V., C. Y. F. Y.], Department of Laboratory Medicine and Pathology [J. C. C.], and Division of Biostatics [S. J. I.], Mayo Clinic/Foundation, Rochester, Minnesota 55905

We profiled the expression of genes in benign and untreated human prostate cancer tissues using oligonucleotide microarrays. We report here 50 genes with distinct expression patterns in metastatic and confined tumors (Gleason score 6 and 9; lymph node invasive and noninvasive). Validation of expression profiles of 6 genes by quantitative PCR revealed a strong inverse correlation in the expression of zinc finger protein 185 (ZNF185), bullous pemphigoid antigen gene (BPAG1), and prostate secretory protein (PSP94) with progression of prostate cancer. Treatment of prostate cancer cell lines with 5-aza-2'-deoxycytidine (5-Aza-CdR), an inhibitor of DNA methylation, restored ZNF185 expression levels. Moreover, methylation-specific PCR confirmed methylation of the 5'CpG islands of the ZNF185 gene in all of the metastatic tissues and 44% of the localized tumor tissues, as well as in the prostate cancer cell lines tested. Thus, transcriptional silencing of ZNF185 by methylation in prostate tumor tissues implicates the ZNF185 gene in prostate tumorigenesis.

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