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

Am J Pathol. 2001 Nov;159(5):1635-43. doi: 10.1016/S0002-9440(10)63010-6.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Carcinoma / genetics*
  • Carcinoma / metabolism*
  • Carcinoma / pathology
  • Caveolin 1
  • Caveolins / genetics*
  • Caveolins / metabolism*
  • Cell Survival / physiology
  • Down-Regulation
  • Female
  • Genes, Tumor Suppressor / physiology*
  • Humans
  • Methylation
  • Oligonucleotide Array Sequence Analysis
  • Ovarian Neoplasms / genetics*
  • Ovarian Neoplasms / metabolism*
  • Ovarian Neoplasms / pathology
  • Phosphorylation
  • Tumor Cells, Cultured


  • CAV1 protein, human
  • Caveolin 1
  • Caveolins