Abstract
To investigate the regulatory mechanism of the expression of the multidrug resistance gene ( mdr-1) and the multidrug resistance-associated protein gene ( mrp), we investigated if p53, WT1, RB, C-myc, N-myc, cyclin D1 and p16 INK4 (p16) are involved in the acquirement of multidrug resistance phenotype (MDR) in human vincristine (VCR)-resistant cells of leukemia/lymphoma cell lines. By using RT-PCR, we observed that MDR in VCR-resistant cell lines was mediated by either mdr-1 or mrp genes. In cells that acquired the overexpression of mdr-1, downregulation of p53 and upregulation of WT-1 were observed. In contrast, no constant change of genes was observed in cells that overexpressed mrp. Although the change in the expression level of cyclin D1 and p-16 accompanied the development of VCR resistance, the mRNA of RB, C-myc and N-myc showed no correlation with the degree of VCR resistance or the level of mdr-1 expression. These results may provide a plausible diagnostic marker for determination of drug sensitivity in cancer patients and suggest that p53 may mediate directly or indirectly the expression of mdr-1 via WT1 in VCR-resistant hematologic cell lines.
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