STABLE EXPRESSION OF THE WILD-TYPE P53 GENE IN HUMAN LUNG-CANCER CELLS AFTER RETROVIRUS-MEDIATED GENE-TRANSFER

A retroviral vector-mediated system was established to allow efficient transduction of the wild-type p53 gene into human lung cancer cell li nes H358a (deleted p53) and H322a (mutant p53). LNSX/p53 constructs in corporating p53 cDNA driven by a beta-actin promoter mediated stable i ntegration of p53. p53 mRNA and protein were detected in these cell li nes 6 months after transduction by Northern and Western blot analyses. Restoration of the wild-type p53 gene suppressed growth in the two tr ansduced cell lines but had no effect in another transduced tumor cell line, H460a, which has an endogenous wild-type p53 gene. A high trans duction efficiency was obtained in cell lines H460a, H322a, and H358a after five cycles of transduction in vitro. Mixing experiments showed that transduced cells could reduce the growth rate of nontransduced ce lls; this reduction may have been mediated by factors shed into the su pernatant of the transduced cell cultures.