∆Np73beta induces caveolin-1 in human non-small cell lung cancer cell line H1299.
Caveolins have recently attracted attention for their possible involvement in signal transduction. Their role in cancer is debated, being reported both a suppressive and oncogenic role in different experimental conditions. Caveolin-1 is regulated by the tumor suppressor p53 which is able to bind its promoter and activate transcription. We had previous evidences indicating that a specific p73 isoform, namely ∆Np73β, when overexpressed in NCI-H1299 induced growth arrest and cell death. By gene expression analysis in cell transiently overexpressed with ∆Np73β, a strong induction of caveolin-1 was found. Caveolin was induced both at mRNA and protein level, and we characterised the promoter sequence of the gene encoding for caveolin-1 and found that the promoter region containing the putative p53 (and hence p73) binding sequence was responsive to ∆Np73β, but not to ∆Np73α and ∆Np73γ which do not induce growth arrest as ∆Np73β does. A reduction in cell adhesion was observed in ∆Np73β overexpressing cells, again supporting a possible role of caveolins in determining these effects. By using specific siRNA directed against human caveolin-1, we could not however antagonize the effects induced by ∆Np73β. Although caveolin-1 represents one of the genes whose expression is strongly activated by ∆Np73β, we could not define a role of caveolin-1 as a mediator of ∆Np73β associated growth arrest. It could well be that the expression of caveolin-1 is able to mediate other activities of ∆Np73β, and studies are in progress to determine whether its expression is mainly associated to metastatic spread.
Laboratory of Molecular Pharmacology, IRCCS-Istituto di Ricerche Farmacologiche "Mario Negri", via G. La Masa 19, 20156, Milan, Italy.
Elisa
E
Caiola
Laboratory of Molecular Pharmacology, IRCCS-Istituto di Ricerche Farmacologiche "Mario Negri", via G. La Masa 19, 20156, Milan, Italy.
Eleonora
E
Marrazzo
Laboratory of Molecular Pharmacology, IRCCS-Istituto di Ricerche Farmacologiche "Mario Negri", via G. La Masa 19, 20156, Milan, Italy.
Simona
S
Alesci
Laboratory of Molecular Pharmacology, IRCCS-Istituto di Ricerche Farmacologiche "Mario Negri", via G. La Masa 19, 20156, Milan, Italy. massimo.broggini@marionegri.it.
Massimo
http://orcid.org/0000-0002-8138-9358
M
Broggini
Laboratory of Molecular Pharmacology, IRCCS-Istituto di Ricerche Farmacologiche "Mario Negri", via G. La Masa 19, 20156, Milan, Italy.
Mirko
M
Marabese
D015153:Blotting, Western; D002289:Carcinoma, Non-Small-Cell Lung / Q000235:genetics*; D051242:Caveolin 1 / Q000096:biosynthesis* / Q000235:genetics; D045744:Cell Line, Tumor; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008175:Lung Neoplasms / Q000235:genetics*; D034741:RNA, Small Interfering; D060888:Real-Time Polymerase Chain Reaction; D014162:Transfection; D000072160:Tumor Protein p73 / Q000235:genetics*
C495540:CAV1 protein, human; D051242:Caveolin 1; D034741:RNA, Small Interfering; D000072160:Tumor Protein p73; C000606369:delta Np73 protein, human
Caveolin-1; Lung; NSCLC; cav-1; p73; ∆Np73