INDUCTION OF APOPTOSIS BUT NOT G(1) ARREST BY EXPRESSION OF THE WILD-TYPE P53 GENE IN SMALL-CELL LUNG-CARCINOMA

Multiple genetic alterations, including inactivation of the p53 and RB genes and loss of heterozygosity on chromosome 3p, occur commonly in small cell lung carcinoma (SOLO). To assess the biological significanc e of p53 inactivation in the development of SCLC, tetracycline (Tc)-in ducible p53 expression plasmids were introduced into a SCLC cell line, N417, in which the p53 gene as well as the RE gene was inactivated, I n the absence (induced) of Tc, cells transfected with the wild-type p5 3 gene formed colonies in 29-58% of those with a mutant p53 gene, Howe ver, wild-type p53 genes were expressed in 0 of 43 transfectants, wher eas mutant p53 genes were expressed in 75% (36/48) of the transfectant s, suggesting that the growth of SCLC cells was suppressed by the expr ession of the wild-type p53 gene, Thus, wild-type p53-inducible clones were further established by transfection in the presence (repressed) of Tc. The in vitro growth was significantly suppressed by the inducti on of wild-type p53 expression, and apoptosis but not G(1) arrest was observed within 24 h of p53 induction, These results strongly suggest that the restoration of the p53 function is sufficient to suppress the growth of SOLO cells in which other genetic alterations remain uncorr ected, and that growth suppression by p53 is due to induction of apopt osis but not due to induction of G(1) arrest through the RB pathway.