Downmodulation of caveolin-1 expression in human ovarian carcinoma is directly related to alpha-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 stu dies in tumor cells independently reported cav-l downregulation and alpha F R overexpression, Here we analysed the expression of the two molecules in n ormal and tumor ovarian samples derived from fresh specimens and from cultu red cell lines. Whereas normal ovary surface epithelial cells displayed onl y cav-l expression, ovarian tumor surgical samples and cell lines (COR, IGR OV1, 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 cD NA transfection, Conversely, cav-l transfection in IGROV1 cells led to down regulated alpha FR expression, together with formation of caveolar structur es and reduction of growth capability, Moreover, cav-l expression was induc ed in IGROV1 cells by transfection with intracellular anti-alpha FR antibod ies to downmodulate alpha FR expression, In cav-l transfected cells, transc riptional 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 transcript ion. Together these results support the notion that alpha FR and cav-l prot ein expression is reciprocally regulated in ovary cancer cells.