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 Safa

Research output: Contribution to journalArticle

32 Citations (Scopus)

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
Externally publishedYes

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Glutamate-Cysteine Ligase
Multidrug Resistance-Associated Proteins
Mesothelioma
Doxorubicin
Cell Line
Genes
P-Glycoprotein
Drug Therapy
Messenger RNA
Malignant Mesothelioma
Antibodies
Pharmaceutical Preparations

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

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

In: International Journal of Cancer, Vol. 75, No. 5, 02.03.1998, p. 757-761.

Research output: Contribution to journalArticle

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AU - Safa, Ahmad

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