a†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 a dagger Np73 beta, when overexpressed in NCI-H1299 induced growth arrest and cell death. By gene expression analysis in cell transiently overexpressed with a dagger Np73 beta, 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 a dagger Np73 beta, but not to a dagger Np73 alpha and a dagger Np73 gamma which do not induce growth arrest as a dagger Np73 beta does. A reduction in cell adhesion was observed in a dagger Np73 beta 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 a dagger Np73 beta. Although caveolin-1 represents one of the genes whose expression is strongly activated by a dagger Np73 beta, we could not define a role of caveolin-1 as a mediator of a dagger Np73 beta associated growth arrest. It could well be that the expression of caveolin-1 is able to mediate other activities of a dagger Np73 beta, and studies are in progress to determine whether its expression is mainly associated to metastatic spread.