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

Oncogene volume 19, pages 4754–4763 (2000)Cite this article

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.

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Acknowledgements

We thank Dr PC Elwood for kindly providing the P1- and P4-CAT constructs and Dr F Mangiarotti for his helpful suggestions. We also thank Mrs A Filippini for technical assistance, Mrs A Cipollina for assistance in preparing the manuscript and Mr M Azzini for photographic reproductions. This work was supported by grants from the Italian Association for Cancer Research (AIRC). M Bagnoli is a recipient of an AIRC/FIRC fellowship.

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Authors and Affiliations

  1. Department of Experimental Oncology, Istituto Nazionale per lo Studio e la Cura dei Tumori, Milan, Italy

    Marina Bagnoli, Antonella Tomassetti, Mariangela Figini, Silvana Canevari & Silvia Miotti

  2. Department of Experimental Medicine, Università di L'Aquila, 67100 L'Aquila, Italy

    Silvio Flati & Vincenza Dolo

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  1. Marina Bagnoli
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  2. Antonella Tomassetti
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  3. Mariangela Figini
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Bagnoli, M., Tomassetti, A., Figini, M. et al. Downmodulation of caveolin-1 expression in human ovarian carcinoma is directly related to α-folate receptor overexpression. Oncogene 19, 4754–4763 (2000). https://doi.org/10.1038/sj.onc.1203839

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