GAIN OF FUNCTION MUTATIONS IN P53

We report that the expression of murine or human mutant p53 proteins i n cells with no endogenous p53 proteins confers new or additional phen otypes upon these cells. Mutant p53 proteins expressed in cell lines l acking p53 resulted in either enhanced tumorigenic potential in nude m ice ((10)3 cells) or enhanced plating efficiency in agar cell culture (human SAOS-2 cells). Also, mutant human p53 alleles, unlike the wild- type p53 protein, could also enhance the expression of a test gene reg ulated by the multi-drug resistance enhancer-promoter element. These d ata demonstrate a gain of function associated with p53 mutations in ad dition to the loss of function shown previously to be associated with mutations in this tumour suppressor gene.