CELL-TYPE-SPECIFIC REGULATION OF P53 EXPRESSION IN NONSMALL CELL LUNG-CARCINOMA CELLS

The expression of an exogenous wild-type p53 protein in different non-small cell lung carcinoma (NSCLC) cell types, harboring endogenous wild-type or mutant p53 or lacking p53 altogether, was investigated to determine whether the status of endogenous p53 protein determined the level of expression of exogenous wild-type p53 protein. NSCLC cells were transfected with wild-type p53 by adenovirus-mediated transfer. When the cells began to express exogenous wild-type p53 protein, the highest levels were observed in p53-null H358 and H1299 cells, whereas the lowest levels, below those of the endogenous wild-type protein, were observed in both H460a and H226b cells. In both H322j and H596b cells, which expressed high levels of endogenous mutant p53, the levels of expression of exogenous wild-type p53 were higher than those in cell lines expressing low levels of endogenous wild-type protein. Northern analyses showed that the differences in the expression of exogenous wild-type p53 protein among the various NSCLC cell lines could not be explained completely by differences in the expression of exogenous p53 mRNA. The results indicated that the level of expression of exogenous wild-type p53 protein in NSCLC cells was determined by the status of endogenous p53. Cell lines that lacked p53 exhibited an intracellular environment more conducive toward overexpression of the protein, in part as a result of differences in the expression of factors that control expression of p53 at the post-transcriptional level.