Assessment of drug-induced dysregulations among seven resistance-associated genes in human tumour cell lines

Anticancer Res. Nov-Dec 1996;16(6B):3531-6.

Abstract

Drug-resistance in cell lines and in malignant human tumours is associated with dysregulation of several genes including mdr1, MRP1, GST-pi, bcl-2, DNA topoisomerase II alpha and beta, and thymidine kinase I. mRNA expression was evaluated by quantitative RT-PCR coupled with HPLC in three human tumour cell lines and drug-resistant (DR)-sublines. DR sublines from RPMI-8226 and KB cells specifically overexpressed the mdr1 gene without major changes observed in other putative DR-associated genes. In contrast, the DR-H69 cells exhibited a 34-fold overexpression of the MRP gene accompanied by significant down-regulation of both DNA topoisomerase II alpha and bcl-2 mRNA gene expression, by factors of 43 and 13 respectively. These results demonstrate the concomitant down regulation of topoisomerase II alpha and bcl-2 genes in response to DR. Furthermore, differential patterns of gene dysregulations appear to vary depending upon both the drug used to select resistance and cellular origin.

MeSH terms

  • DNA Topoisomerases, Type II / metabolism
  • DNA-Binding Proteins / metabolism
  • Drug Resistance, Neoplasm / genetics*
  • Gene Expression Regulation, Neoplastic / drug effects
  • Genes, MDR / drug effects*
  • Glutathione Transferase / metabolism
  • Humans
  • Isoenzymes / metabolism
  • Multidrug Resistance-Associated Proteins*
  • MutS Homolog 3 Protein
  • Neoplasm Proteins / metabolism*
  • Proto-Oncogene Proteins c-bcl-2 / metabolism
  • RNA, Messenger / metabolism*
  • Thymidine Kinase / metabolism
  • Tumor Cells, Cultured / drug effects

Substances

  • DNA-Binding Proteins
  • Isoenzymes
  • MSH3 protein, human
  • Multidrug Resistance-Associated Proteins
  • MutS Homolog 3 Protein
  • Neoplasm Proteins
  • Proto-Oncogene Proteins c-bcl-2
  • RNA, Messenger
  • Glutathione Transferase
  • Thymidine Kinase
  • thymidine kinase 1
  • DNA Topoisomerases, Type II
  • multidrug resistance-associated protein 1