Downmodulation of caveolin-1 expression in human ovarian carcinoma is directly related to α-folate receptor overexpression

Marina Bagnoli, Antonella Tomassetti, Mariangela Figini, Silvio Flati, Vincenza Dolo, Silvana Canevari, Silvia Miotti

Research output: Contribution to journalArticle

Abstract

Caveolin (cav-1) and the GPI-anchored α-folate receptor (αFR) are membrane proteins both found associated to caveolar structures. Several studies in tumor cells independently reported cav-1 downregulation and αFR overexpression. Here we analysed the expression of the two molecules in normal and tumor ovarian samples derived from fresh specimens and from cultured cell lines. Whereas normal ovary surface epithelial cells displayed only cav-1 expression, ovarian tumor surgical samples and cell lines (COR, IGROV1, OVCAR3 and OVCA432) displayed high αFR and low-level or no cav-1 expression, except those cell lines (SKOV3 and SW626) with the lower αFR expression. SKOV3, but not two αFR-negative non-ovarian cell lines, exhibited downregulation of cav-1 expression following stable αFR cDNA transfection. Conversely, cav-1 transfection in IGROV1 cells led to downregulated αFR expression, together with formation of caveolar structures and reduction of growth capability. Moreover, cav-1 expression was induced in IGROV1 cells by transfection with intracellular anti-αFR antibodies to downmodulate αFR expression. In cav-1 transfected cells, transcriptional activity of the αFR-specific promoter P1 was reduced by 70% and an additional specific DNA-protein complex was identified by gel-shift assay, indicating that cav-1 expression influences αFR gene transcription. Together these results support the notion that αFR and cav-1 protein expression is reciprocally regulated in ovary cancer cells.

Original languageEnglish
Pages (from-to)4754-4763
Number of pages10
JournalOncogene
Volume19
Issue number41
Publication statusPublished - Sep 28 2000

    Fingerprint

Keywords

  • α-folate receptor
  • Caveolin
  • Ovarian cancer
  • Transcriptional regulation

ASJC Scopus subject areas

  • Cancer Research
  • Genetics
  • Molecular Biology

Cite this