PHENOTYPIC ALTERATIONS OF SMALL-CELL LUNG-CARCINOMA INDUCED BY DIFFERENT LEVELS OF WILD-TYPE P53 EXPRESSION

p53 induces both growth arrest and apoptosis in cancer cells, To clari fy whether the level of p53 expression determines the response of smal l cell lung carcinoma (SCLC) cells, we assessed the effect of various p53 levels on a p53-null SCLC cell line, N417, using a tetracycline (T c)-regulated inducible p53 expression system, Apoptosis was induced in SCLC cells with high p53 expression. Although low levels of p53 induc ed G1 arrest accompanied by p21 expression, cells with G1 arrest seeme d to undergo apoptosis after further cultivation, Expression of exogen ous p21 induced G1 arrest but not apoptosis in SCLC cells, suggesting that p53-mediated G1 arrest was induced through p21 expression, Moreov er, high level of p53 expression down regulated Bcl-2 expression in SC LC cells, while Bax was consistently expressed irrespective to the lev el of p53 expression, These results suggest that p53-mediated apoptosi s and G1 arrest depend on level of p53 expression in SCLC cells and th at the relative dominancy of Bar to Bcl-2 is involved in the induction of apoptosis by high level of p53 expression.