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

Elena Sanna, Silvia Miotti, Mimma Mazzi, Giuseppina De Santis, Silvana Canevari, Antonella Tomassetti

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish
Pages (from-to)1307-1317
Number of pages11
JournalExperimental Cell Research
Volume313
Issue number7
DOIs
Publication statusPublished - Apr 15 2007

Keywords

  • Caveolin-1
  • Cyclin D1
  • Folate receptor
  • Gene transcription
  • Ovarian carcinoma

ASJC Scopus subject areas

  • Cell Biology

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