title: Caveolin-1 is down-regulated in human ovarian carcinoma and acts as a candidate tumor suppressor gene.
abstract: 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.
authors.affiliation: Institute of Pathology, Charité, Humboldt University Berlin, Berlin, Germany.
authors.forename: K
authors.initials: K
authors.lastname: Wiechen
authors.forename: L
authors.initials: L
authors.lastname: Diatchenko
authors.forename: A
authors.initials: A
authors.lastname: Agoulnik
authors.forename: K M
authors.initials: KM
authors.lastname: Scharff
authors.forename: H
authors.initials: H
authors.lastname: Schober
authors.forename: K
authors.initials: K
authors.lastname: Arlt
authors.forename: B
authors.initials: B
authors.lastname: Zhumabayeva
authors.forename: P D
authors.initials: PD
authors.lastname: Siebert
authors.forename: M
authors.initials: M
authors.lastname: Dietel
authors.forename: R
authors.initials: R
authors.lastname: Schäfer
authors.forename: C
authors.initials: C
authors.lastname: Sers
mesh_terms: D002277:Carcinoma / Q000235:genetics* / Q000378:metabolism* / Q000473:pathology; D051242:Caveolin 1; D022461:Caveolins / Q000235:genetics* / Q000378:metabolism*; D002470:Cell Survival / Q000502:physiology; D015536:Down-Regulation; D005260:Female; D016147:Genes, Tumor Suppressor / Q000502:physiology*; D006801:Humans; D008745:Methylation; D020411:Oligonucleotide Array Sequence Analysis; D010051:Ovarian Neoplasms / Q000235:genetics* / Q000378:metabolism* / Q000473:pathology; D010766:Phosphorylation; D014407:Tumor Cells, Cultured
chemical_list: C495540:CAV1 protein, human; D051242:Caveolin 1; D022461:Caveolins