Expression of apoptosis-related genes in human head and neck squamous cellcarcinomas undergoing p53-mediated programmed cell death

Human head and neck squamous cell carcinoma (HNSCC) lines infected with a r eplication-defective Ad5CMV-p53 vector bearing a wild-type human p53 gene w ere used to examine alterations in the production of proteins implicated in regulating apoptosis. Because HNSCC Lines express abundant levels of c-myc , and simultaneous expression of c-myc and p53 is known to trigger apoptosi s in other cells, cooperation between these two genes was examined. Surpris ingly, levels of c-myc mRNA and protein were rapidly and profoundly suppres sed after infection,vith wildtype p53, Suppression of c-myc using antisense oligodeoxynucleotides (in the absence of p53) was sufficient to trigger ap optosis in Tu-138 cells, raising the possibility that the reduction of c-my c may be involved in at least one of the cell death pathways mediated by p5 3, Expression of a panel of Bcl-2 homology proteins was also examined in HN SCC Lines undergoing p53-mediated apoptosis, No changes in Bcl-2, Bak, or B cl-x(S) were found after p53 expression. Increased levels of the apoptosis- accelerating protein Bar were found in HNSCC lines after infection with Ad5 CMV-p53, induction of the apoptosis-inhibiting protein Bcl-x(L) was observe d in Tu-167 cells and may account for the delayed onset of apoptosis in the se cells, These studies suggest that multiple pathways may regulate apoptos is after transient overexpression of p53.