INTRODUCTION OF WILD-TYPE P53 GENE DOWN-REGULATES THE EXPRESSION OF H-RAS GENE AND SUPPRESSES THE GROWTH OF BLADDER-CANCER CELLS

Retroviral vectors were used to introduce the wild-type p53 gene into human bladder cancer cell lines BIU-87 and EJ, which express endogenou s wt-p53 gene and have a mutation in H-ras gene. The expression of the exogenous wt-p53 gene in cells suppresses the growth of the bladder c ancer cells in standard culture and in soft agar and blocks the cell c ycle progression in G1. The BIU-87 and EJ cells developed tumors with average volumes of 6.53 cm(3) and 6.61 cm(3) in nude mice in 9 weeks a fter inoculation, while the cells transduced with wt-p53 gene failed t o form tumors. The expression of H-ras gene in bladder cancer cells wa s reduced at mRNA level. These results suggest that the overexpression of the wt-p53 gene suppresses the expression of mutant H-ms gene and inhibits the tumor cell growth in vivo and in vitro.