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

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