Caveolin-1 is down-regulated in human ovarian carcinoma and acts as a candidate tumor suppressor gene

To identify novel markets differentially expressed in ovarian cancer versus normal ovary, we hybridized microarrays with cDNAs derived from normal hum an ovaries and advanced stage ovarian carcinomas. This analysis revealed do wn-regulation of the caveolin-1 gene (CAV1) in ovarian carcinoma samples. S uppression of CAV1 in ovarian carcinomas was confirmed using a tumor tissue army consisting of 68 cDNA pools from different matched human tumor and no rmal tissues. Immunohistochemistry demonstrated expression of caveolin-1 in normal and benign ovarian epithelial cells, but loss of expression in sero us ovarian carcinomas. In low-grade carcinomas, redistribution of caveolin- 1 from a membrane-associated pattern observed in normal epithelium to a cyt oplasmic localization pattern was observed. No expression of caveolin-1 was detectable in four of six ovarian carcinoma cell lines investigated. In SK OV-3 and ES-2 carcinoma cells, which express high levels of the caveolin-1 protein, phosphorylation of the 22-kd caveolin-1 isoform was detected. Inhi bition of both DNA methylation and histone deacetylation using 5-aza-2'deox ycytidine and Trichostatin A, respectively, relieves down-regulation of cav eolin-1 in OAW42 and OVCAR-3 cells which is in part mediated by direct regu lation at the mRNA level. Expression of CAV1 in the ovarian carcinoma cell line OVCAR-3, resulted in suppression of tumor cell survival in vitro, sugg esting that the CAV1 gene is likely to act as a tumor suppressor gene in hu man ovarian epithelium.