Modulation of Activity of the Promoter of the Human MDR 1 Gene by Ras and p53

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Abstract
Drug resistance in human cancer is associated with overexpression of the multidrug resistance ( MDR 1) gene, which confers cross-resistance to hydrophobic natural product cytotoxic drugs. Expression of the MDR 1 gene can occur de novo in human cancers in the absence of drug treatment. The promoter of the human MDR 1 gene was shown to be a target for the c-Ha-Ras-1 oncogene and the p53 tumor suppressor gene products, both of which are associated with tumor progression. The stimulatory effect of c-Ha-Ras-1 was not specific for the MDR 1 promoter alone, whereas a mutant p53 specifically stimulated the MDR 1 promoter and wild-type p53 exerted specific repression. These results imply that the MDR 1 gene could be activated during tumor progression associated with mutations in Ras and p53.