Downmodulation of caveolin-1 expression in human ovarian carcinoma is directly related to α-folate receptor overexpression
- 28 September 2000
- journal article
- research article
- Published by Springer Science and Business Media LLC in Oncogene
- Vol. 19 (41), 4754-4763
- https://doi.org/10.1038/sj.onc.1203839
Abstract
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.Keywords
This publication has 33 references indexed in Scilit:
- Reciprocal Regulation of Neu Tyrosine Kinase Activity and Caveolin-1 Protein Expression in Vitro and in VivoPublished by Elsevier BV ,1998
- THE CAVEOLAE MEMBRANE SYSTEMAnnual Review of Biochemistry, 1998
- Interaction of a Receptor Tyrosine Kinase, EGF-R, with Caveolins: CAVEOLIN BINDING NEGATIVELY REGULATES TYROSINE AND SERINE/THREONINE KINASE ACTIVITIESPublished by Elsevier BV ,1997
- Two sterol regulatory element-like sequences mediate up-regulation of caveolin gene transcription in response to low density lipoprotein free cholesterolProceedings of the National Academy of Sciences of the United States of America, 1997
- Recombinant Expression of Caveolin-1 in Oncogenically Transformed Cells Abrogates Anchorage-independent GrowthPublished by Elsevier BV ,1997
- Identification of Peptide and Protein Ligands for the Caveolin-scaffolding DomainPublished by Elsevier BV ,1997
- The Divergent 5‘ Termini of the α Human Folate Receptor (hFR) mRNAs Originate from Two Tissue-Specific Promoters and Alternative Splicing: Characterization of the α hFR Gene StructureBiochemistry, 1997
- Folate ReceptorsAnnual Review of Nutrition, 1996
- Potocytosis: Sequestration and Transport of Small Molecules by CaveolaeScience, 1992
- The Ca-MOv18 molecule, a cell-surface marker of human ovarian carcinomas, is anchored to the cell membrane by phosphatidylinositolBiochemical and Biophysical Research Communications, 1990