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Title: Binding of nuclear caveolin-1 to promoter elements of growth-associated genes in ovarian carcinoma cells

Abstract

Caveolin-1 (cav-1), a member of a protein family associated mainly with cell membrane microdomains in many cell types, acts as a tumor suppressor in ovarian carcinoma cells. Biochemical analyses demonstrated that cav-1 was also localized in the nuclei of ovarian carcinoma cells, endogenously (SKOV3) or ectopically (IGtC3) expressing cav-1. By confocal analyses, the same cell lines as well as IGROV1 and SKOV3 cells transiently transfected with green fluorescent protein-cav-1 fusion protein showed nuclear punctate speckled pattern. Subnuclear distribution analysis revealed cav-1 mainly associated with the nuclear matrix, but also slightly with chromatin. Cav-1 was found in nuclear high-molecular weight complexes and by confocal analysis was found to co-localized with the inner nuclear membrane protein emerin. Cyclin D1 and folate receptor promoters were modulated by cav-1 in SKOV3 cells as demonstrated by transient transfection with or silencing of cav-1. Chromatin immunoprecipitation and supershift assays indicated that nuclear cav-1 can bind in vitro and in vivo to promoter sequences of both cyclin D1 and folate receptor genes. These data suggest that in ovarian carcinoma cells cav-1, localized in transcriptionally inactive chromatin, exerts a functional activity mediated, at least in part, by directly binding to sequences of genes involved in proliferation.

Authors:
 [1];  [2];  [1];  [1];  [1];  [1]
  1. Unit of Molecular Therapies, Department of Experimental Oncology, Istituto Nazionale Tumori, 20133, Milan (Italy)
  2. Unit of Molecular Therapies, Department of Experimental Oncology, Istituto Nazionale Tumori, 20133, Milan (Italy). E-mail: silvia.miotti@istitutotumori.mi.it
Publication Date:
OSTI Identifier:
20972138
Resource Type:
Journal Article
Resource Relation:
Journal Name: Experimental Cell Research; Journal Volume: 313; Journal Issue: 7; Other Information: DOI: 10.1016/j.yexcr.2007.02.005; PII: S0014-4827(07)00055-9; Copyright (c) 2007 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved; Country of input: International Atomic Energy Agency (IAEA)
Country of Publication:
United States
Language:
English
Subject:
60 APPLIED LIFE SCIENCES; CALVES; CARCINOMAS; CELL MEMBRANES; CHROMATIN; DETERGENTS; ELECTROPHORESIS; ENDOPLASMIC RETICULUM; GELS; GENES; IN VITRO; MONOCLONAL ANTIBODIES; RECEPTORS; SODIUM; TRITONS

Citation Formats

Sanna, Elena, Miotti, Silvia, Mazzi, Mimma, De Santis, Giuseppina, Canevari, Silvana, and Tomassetti, Antonella. Binding of nuclear caveolin-1 to promoter elements of growth-associated genes in ovarian carcinoma cells. United States: N. p., 2007. Web. doi:10.1016/j.yexcr.2007.02.005.
Sanna, Elena, Miotti, Silvia, Mazzi, Mimma, De Santis, Giuseppina, Canevari, Silvana, & Tomassetti, Antonella. Binding of nuclear caveolin-1 to promoter elements of growth-associated genes in ovarian carcinoma cells. United States. doi:10.1016/j.yexcr.2007.02.005.
Sanna, Elena, Miotti, Silvia, Mazzi, Mimma, De Santis, Giuseppina, Canevari, Silvana, and Tomassetti, Antonella. Sun . "Binding of nuclear caveolin-1 to promoter elements of growth-associated genes in ovarian carcinoma cells". United States. doi:10.1016/j.yexcr.2007.02.005.
@article{osti_20972138,
title = {Binding of nuclear caveolin-1 to promoter elements of growth-associated genes in ovarian carcinoma cells},
author = {Sanna, Elena and Miotti, Silvia and Mazzi, Mimma and De Santis, Giuseppina and Canevari, Silvana and Tomassetti, Antonella},
abstractNote = {Caveolin-1 (cav-1), a member of a protein family associated mainly with cell membrane microdomains in many cell types, acts as a tumor suppressor in ovarian carcinoma cells. Biochemical analyses demonstrated that cav-1 was also localized in the nuclei of ovarian carcinoma cells, endogenously (SKOV3) or ectopically (IGtC3) expressing cav-1. By confocal analyses, the same cell lines as well as IGROV1 and SKOV3 cells transiently transfected with green fluorescent protein-cav-1 fusion protein showed nuclear punctate speckled pattern. Subnuclear distribution analysis revealed cav-1 mainly associated with the nuclear matrix, but also slightly with chromatin. Cav-1 was found in nuclear high-molecular weight complexes and by confocal analysis was found to co-localized with the inner nuclear membrane protein emerin. Cyclin D1 and folate receptor promoters were modulated by cav-1 in SKOV3 cells as demonstrated by transient transfection with or silencing of cav-1. Chromatin immunoprecipitation and supershift assays indicated that nuclear cav-1 can bind in vitro and in vivo to promoter sequences of both cyclin D1 and folate receptor genes. These data suggest that in ovarian carcinoma cells cav-1, localized in transcriptionally inactive chromatin, exerts a functional activity mediated, at least in part, by directly binding to sequences of genes involved in proliferation.},
doi = {10.1016/j.yexcr.2007.02.005},
journal = {Experimental Cell Research},
number = 7,
volume = 313,
place = {United States},
year = {Sun Apr 15 00:00:00 EDT 2007},
month = {Sun Apr 15 00:00:00 EDT 2007}
}
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