Hypermethylation of the caveolin-1 gene promoter in prostate cancer

BACKGROUND. Hypermethylation of CpG islands in the promoter regions of tumo r suppressor genes is one mechanism of tumorigenesis. Caveolin-1 (Cav-1), a gene coding for the structural component of cellular caveolae, is involved in cell signaling and has been proposed to be a tumor suppressor gene in s everal malignancies. This gene maps to 7q31.1, a site known to be deleted i n some prostate tumors. We chose to examine the methylation status of the p romoter region of Cav-1 to determine whether this gene could function as a tumor suppressor in prostate cancer. METHODS. Genomic DNA. from both tumor and normal prostate epithelial cells was obtained from paraffin-embedded prostate sections by laser capture micr odissection (LCM). The methylation status of 24 CpG sites at the 5' promote r region of Cav-1 was analyzed by bisulfite-direct-sequencing after amplifi cation by PCR using primers specific for bisulfate modified DNA. Immunohist ochemistry staining with a cav-1-specific antibody was also performed to ev aluate the expression of the gene. RESULTS. Twenty of the 22 (90.9%) informative cases showed promoter hyperme thylation in the tumor cell population when compared with adjacent normal p rostate cells with an average Methylation Index (potential frequency of tot al possible methylated Cs) from tumor cells equal to 0.426 vs. 0.186 for no rmal cells (P = 0.001). While no association with Gleason grade was found, overall increased methylation correlated with PSA failure (P = 0.016), sugg estive of clinical recurrence. Elevated immunoreactivity with a Cav-1 antib ody was observed in tumor cells from 7 of 26 prostate samples tested; this was associated with a Gleason score but not correlated with PSA failure or Methylation Index. CONCLUSIONS. CPG sites at the 5' promoter of Cav-1 are more methylated in t umor than in adjacent normal prostate cells. Hypermethylation of the Cav-1 promoter supports the notion that Cav-1 may function as a tumor suppressor gene in prostate cancer and evidence is presented suggesting that methylati on status of this gene is not only a marker for cancer but also may be pred ictive of outcome. (C) 2001 Wiley-Liss, Inc.