EXPRESSION PATTERNS OF MULTIDRUG-RESISTANCE (MDR1), MULTIDRUG RESISTANCE-ASSOCIATED PROTEIN (MRP), GLUTATHIONE-S-TRANSFERASE-PI (GST-PI) AND DNA TOPOISOMERASE-II (TOPO-II) GENES IN RENAL-CELL CARCINOMAS AND NORMAL KIDNEY

Purpose: Expression levels of the multidrug-resistance (mdr1), multidr ug resistance-associated protein (MRP), glutathione-S-transferase-pi ( GST-pi) and DNA topoisomerase II (Topo II) genes in normal kidney and renal cell carcinomas were analyzed to study the complexity of the rol es of these genes. Materials and Methods: The reverse transcription-po lymerase chain reaction (RT-PCR) assay was used with beta(2) microglob ulin (beta(2) m) as the internal control. Results: In normal kidneys, the expression levels of the 4 genes in individual normal kidney sampl es correlated significantly with one another. Comparisons of the expre ssion levels between normal kidneys and renal cell carcinomas showed t hat only the mean MRP gene expression level was higher in renal cell c arcinomas than in normal kidneys (p = 0.018). The expression patterns of the 4 genes in renal cell carcinomas differed markedly for nonpapil lary and papillary tumors. The mean MRP/beta(2) m ratio for the papill ary type was significantly lower than that for the nonpapillary alveol ar type carcinoma (p = 0.004). The 4 genes showed moderate positive co rrelations with one another in alveolar type renal carcinoma similar t o the correlations observed in normal kidneys. In contrast, in papilla ry type, MRP expression was inversely correlated with mdr1 and Topo II expression. Conclusion: Differences in cytogenetic changes, origins a nd natural histories between papillary and nonpapillary carcinoma may be associated with these distinct expression patterns of the resistanc e-related genes. Further study is required to clarify whether the diff erences in the expression patterns between these 2 structural types of carcinoma affect their chemosensitivities and clinical outcomes.