Co-ordinated over-expression of the MRP and gamma-glutamylcysteine synthetase genes, but not MDR1, correlates with doxorubicin resistance in human malignant mesothelioma cell lines

Int J Cancer. 1998 Mar 2;75(5):757-61. doi: 10.1002/(sici)1097-0215(19980302)75:5<757::aid-ijc15>3.0.co;2-3.

Abstract

While human malignant mesothelioma is extremely resistant to chemotherapy, its intrinsic resistance mechanisms remain largely unknown. In this study, we used normal human mesothelial cells and 5 human mesothelioma cell lines not previously exposed to chemotherapeutic agents to demonstrate that the mRNA for the multidrug resistance-associated protein (MRP) and gamma-glutamylcysteine synthetase (gamma-GCSh) heavy subunit genes, but not the P-glycoprotein (MDR1) gene, are co-ordinately over-expressed in mesothelioma cell lines. Expression of MRP as detected with an anti-MRP antibody correlated with decreased doxorubicin accumulation and resistance of mesothelioma cells to this drug. Our results strongly suggest roles for MRP and gamma-GCSh in chemoresistance in mesotheliomas.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • ATP Binding Cassette Transporter, Subfamily B, Member 1 / genetics*
  • ATP-Binding Cassette Transporters / genetics*
  • Doxorubicin / pharmacology*
  • Drug Resistance, Neoplasm*
  • Epithelium / metabolism
  • Gene Expression
  • Glutamate-Cysteine Ligase / genetics*
  • Humans
  • Mesothelioma / drug therapy
  • Mesothelioma / enzymology
  • Mesothelioma / metabolism*
  • Multidrug Resistance-Associated Proteins
  • RNA, Messenger / genetics
  • RNA, Neoplasm / genetics
  • Tumor Cells, Cultured

Substances

  • ATP Binding Cassette Transporter, Subfamily B, Member 1
  • ATP-Binding Cassette Transporters
  • Multidrug Resistance-Associated Proteins
  • RNA, Messenger
  • RNA, Neoplasm
  • Doxorubicin
  • Glutamate-Cysteine Ligase