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 (alphaFR) are membrane proteins both found associated to caveolar structures. Several studies in tumor cells independently reported cav-1 downregulation and alphaFR 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 alphaFR and low-level or no cav-1 expression, except those cell lines (SKOV3 and SW626) with the lower alphaFR expression. SKOV3, but not two alphaFR-negative non-ovarian cell lines, exhibited down-regulation of cav-1 expression following stable alphaFR cDNA transfection. Conversely, cav-1 transfection in IGROV1 cells led to downregulated alphaFR 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-alphaFR antibodies to downmodulate alphaFR expression. In cav-1 transfected cells, transcriptional activity of the alphaFR-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 alphaFR gene transcription. Together these results support the notion that alphaFR and cav-1 protein expression is reciprocally regulated in ovary cancer cells.
Bagnoli
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Department of Experimental Oncology, Istituto Nazionale per lo Studio e la Cura dei Tumori, Milan, Italy.
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D016475:3T3 Cells; D000818:Animals; D002277:Carcinoma / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D002294:Carcinoma, Squamous Cell / Q000473:pathology; D002352:Carrier Proteins / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D021941:Caveolae / Q000648:ultrastructure; D051242:Caveolin 1; D022461:Caveolins / Q000096:biosynthesis* / Q000235:genetics; D004273:DNA, Neoplasm / Q000235:genetics / Q000378:metabolism; D005260:Female; D058973:Folate Receptors, GPI-Anchored; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D046911:Macromolecular Substances; D051379:Mice; D009363:Neoplasm Proteins / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D010051:Ovarian Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D011401:Promoter Regions, Genetic; D011956:Receptors, Cell Surface; D014162:Transfection; D014407:Tumor Cells, Cultured / Q000378:metabolism; D014846:Vulvar Neoplasms / Q000473:pathology
C495540:CAV1 protein, human; D002352:Carrier Proteins; C495541:Cav1 protein, mouse; D051242:Caveolin 1; D022461:Caveolins; D004273:DNA, Neoplasm; D058973:Folate Receptors, GPI-Anchored; D046911:Macromolecular Substances; D009363:Neoplasm Proteins; D011956:Receptors, Cell Surface