P53 PROTEIN EXPRESSION IN HUMAN MULTIDRUG-RESISTANT CEM LYMPHOBLASTS

A role for p53 in the regulation of multidrug-resistance (MDR) has bee n postulated as wild-type p53 suppresses and mutant p53 specifically a ctivates the mdr? promoter. Moreover, changes in p53 expression and/or functions could be implicated in drug resistance. As the parental lym phoblastic CCRF-CEM cell line has been described as expressing a mutat ed form of p53, we have examined p53 and mdm2 protein levels in the hu man multidrug-resistant CEM-VLB cell line variant. These drug-resistan t CEM-VLB cells, which have increased expressions of mdr1 and P-glycop rotein, displayed p53 and mdm2 protein expressions similar to those ob served in their sensitive CCRF-CEM counterparts. Treatment of these dr ug-resistant cells with non-toxic doses of the resistance-inducing dru g vinblastin induced a strong increase in p53 protein and mRNA but was ineffective on mdm2 protein expression, or mdr1 mRNA expression. Thes e data indicate that mutant p53 protein was not overexpressed in these MDR cells. This overexpression could be induced by microtubule-active drug treatment, but, as previously observed in other sensitive cell l ines, mutant p53 from these MDR cells was unable to positively regulat e mdm2 gene product expression. (C) 1997 Elsevier Science Ltd.