TY - JOUR
T1 - Binding of nuclear caveolin-1 to promoter elements of growth-associated genes in ovarian carcinoma cells
AU - Sanna, Elena
AU - Miotti, Silvia
AU - Mazzi, Mimma
AU - De Santis, Giuseppina
AU - Canevari, Silvana
AU - Tomassetti, Antonella
PY - 2007/4/15
Y1 - 2007/4/15
N2 - 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.
AB - 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.
KW - Caveolin-1
KW - Cyclin D1
KW - Folate receptor
KW - Gene transcription
KW - Ovarian carcinoma
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UR - http://www.scopus.com/inward/citedby.url?scp=33947729030&partnerID=8YFLogxK
U2 - 10.1016/j.yexcr.2007.02.005
DO - 10.1016/j.yexcr.2007.02.005
M3 - Article
C2 - 17359972
AN - SCOPUS:33947729030
VL - 313
SP - 1307
EP - 1317
JO - Experimental Cell Research
JF - Experimental Cell Research
SN - 0014-4827
IS - 7
ER -