Simian virus 40 T antigen induces p53-independent apoptosis but does not suppress erbB2/neu gene expression in immortalized human epithelial cells

Previously, we have shown that simian virus 40 (SV40) T antigen can directl y cause apoptosis in immortalized human epithelial cells under normal growt h conditions. In this study, we further characterized the mechanism of T-an tigen-mediated apoptosis involving p53 and whether T antigen can suppress e rbB2/neu gene expression. Our results show the differential regulation of e rbB2/neu gene expression in different cell clones in response to T antigen transgene, indicating that the regression of erbB2/neu gene by SV40 T is ce ll-type dependent. Our previous study reported T-antigen-induced apoptosis in p53 mutant cells; however, in this study we find increased levels of p53 protein in T-antigen-containing cells. Therefore, we examined the transact ivation function of p53 in these cells. Our data show the failure to transa ctivate p53, suggesting that increased p53 protein in T antigen expressing cells is functionless at least for transcriptional activation. (C) 1999 Els evier Science Ireland Ltd. All rights reserved.