To identify novel markers differentially expressed in ovarian cancer versus normal ovary, we hybridized microarrays with cDNAs derived from normal human ovaries and advanced stage ovarian carcinomas. This analysis revealed down-regulation of the caveolin-1 gene (CAV1) in ovarian carcinoma samples. Suppression of CAV1 in ovarian carcinomas was confirmed using a tumor tissue array consisting of 68 cDNA pools from different matched human tumor and normal tissues. Immunohistochemistry demonstrated expression of caveolin-1 in normal and benign ovarian epithelial cells, but loss of expression in serous ovarian carcinomas. In low-grade carcinomas, redistribution of caveolin-1 from a membrane-associated pattern observed in normal epithelium to a cytoplasmic localization pattern was observed. No expression of caveolin-1 was detectable in four of six ovarian carcinoma cell lines investigated. In SKOV-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. Inhibition of both DNA methylation and histone deacetylation using 5-aza-2'deoxycytidine and Trichostatin A, respectively, relieves down-regulation of caveolin-1 in OAW42 and OVCAR-3 cells which is in part mediated by direct regulation at the mRNA level. Expression of CAV1 in the ovarian carcinoma cell line OVCAR-3, resulted in suppression of tumor cell survival in vitro, suggesting that the CAV1 gene is likely to act as a tumor suppressor gene in human ovarian epithelium.

Caveolae are 50-to 100-nm -shaped invaginations of the plasma membrane that have been implicated in endocytosis and signal transduction.1 Caveolae membranes are enriched with specific lipids (glycosphingolipids, sphingomyelin, and cholesterol) and different lipidmodified signaling molecules.2 Caveolins, a family of highly conserved 20-to 25-kd integral membrane proteins, are the principal protein component of caveolae. Thus far the mammalian caveolin family consists of four proteins, caveolin-1[␣], -1[␤], -2, and -3 encoded by three genes. Caveolins-1 and -2 are co-expressed, whereas the expression of caveolin-3 is muscle-specific.

Depletion of miRNA-210 disrupts photoreceptor integrity and visual function in Drosophila melanogaster.