Expression of multidrug resistance-related genes (mdrl, MRP, GST-π and DNA topoisomerase II) in urothelial cancers

W. J. Kim, Y. Kakehi, W. J. Wu, M. Fukumoto, O. Yoshida

Research output: Contribution to journalArticlepeer-review

23 Citations (Scopus)

Abstract

Objective: To characterize the multidrug resistance (MDR) phenotype in human urothelial cancers, the expression levels of four MDR-related genes (multidrug resistance, mdrl; multidrug resistance-associated protein, MRP; glutathione S-transferase-π. GST-π; and DNA topoisomerase II, topo II) were analysed in urothelial cancers. Materials and methods: Fifty-two tumour tissue and three normal urothelial mucosa samples were obtained from 44 patients with urothelial cancers. The expression of each gene was analysed with a reverse-transcription polymerase chain reaction (RT-PCR) method using β2-microglobulin (b2m) mRNA as an endogenous control. Levels of expression were expressed as the ratio of the specific products of the target gene to those specific to b2m. Results: In primary urothelial cancer tissues, the mean (SD) expression of mdrl, MRP, GST-π and topo II relative to b2m expression were 0.067 (0.061), 0.27 (0.23), 0.35 (0.31) and 0.12 (0.05), respectively. The mean expressions of MRP and GST-π were higher than those of mdrl and topo II. The mean ratios of mdrl/b2m, MRP/b2m, GST-π/b2m and topo II/b2m in normal urothelial mucosa were 0.06 (0.03), 0.12 (0.09), 0.30 (0.32) and 0.14 (0.01), respectively. There was no significant association of the expression of each gene with either the grade or extent of the primary tumour. The level of MRP expression in each sample was correlated significantly with the expression of mdrl and GST-π in the urothelial cancers (r=0.637 and 0.537, respectively). Chemotherapy did not markedly influence the induction of expression of the MDR-related genes, except for one case in which mdrl expression was 15 times greater than before chemotherapy. The expression of GST-π in the patients not receiving chemotherapy was significantly higher than in those that did. Conclusions: These results suggest that the activation of MRP and GST-π expression occurs during the tumorigenesis of urothelial cancers and that it may confer de novo and acquired drug resistance on urothelial cancers. These results should provide further insight into the complex role postulated for MDR-related genes in chemotherapy, carcinogenesis and tumour progression.

Original languageEnglish
Pages (from-to)361-368
Number of pages8
JournalBritish Journal of Urology
Volume78
Issue number3
Publication statusPublished - 1996 Dec 1

Keywords

  • Gene expression
  • Multidrug resistance-related genes
  • Urothelial cancer

ASJC Scopus subject areas

  • Urology

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