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

Besim Ogretmen, Hamid R. Bahadori, Mary D. Mccauley, Alice Boylan, Mark R. Green, Ahmad R. Safa

Research output: Contribution to journalArticlepeer-review

32 Scopus citations

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 γ- glutamylcysteine synthetase (γ-GCS(h)) 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 γ-GCS(h) in chemoresistance in mesotheliomas.

Original languageEnglish (US)
Pages (from-to)757-761
Number of pages5
JournalInternational Journal of Cancer
Volume75
Issue number5
DOIs
StatePublished - Mar 2 1998

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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