Cell type-specific induction and alternative splicing of the Bax gene mediated by p53.

The expression of Bax mRNA products was investigated in five different cell types that were induced to overexpress the p53 protein. Colon (HT29), lung (H358), prostate (PC-3), and endothelial (ECV-304) transformed cells lines and primary human umbilical vein endothelial cells (HUVEC) were infected with a p53 recombinant adenovirus. The expression of Bax transcripts in p53-induced cells was investigated by reverse-transcription polymerase chain reaction (RT-PCR). The Bax mRNA species was detected in all cell types and was induced in response to p53 overexpression in the colon, lung, and prostate cell lines. In contrast, Bax expression was reduced several-fold in ECV-304 endothelial cells overproducing p53. The Bax spliced transcript was induced by p53 in the ECV-304, PC-3, and HT29 cells, but not in H358 cells. Bax was the predominant species expressed in primary HUVEC endothelial cells but, in contrast to the immortalized ECV-304 endothelial cell line, induction of p53 failed to alter the expression of Bax or to induce any other Bax transcripts. Furthermore, HUVEC were more resistant to induction of apoptosis by overexpression of p53 than ECV-304 cells, suggesting a role for Bax in endothelial cell apoptosis. The results implicate cell type-specific factors as playing important roles in the induction and alternative splicing of the Bax gene by p53.

Cell type-specific induction and alternative splicing of the Bax gene mediated by p53. Academic Article