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Co‐ordinated over‐expression of the MRP and γ‐glutamylcysteine synthetase genes, but not MRD1, correlates with doxorubicin resistance in human malignant mesothelioma cell lines
Author(s) -
Ogretmen Besim,
Bahadori Hamid R.,
McCauley Mary D.,
Boylan Alice,
Green Mark R.,
Safa Ahmad R.
Publication year - 1998
Publication title -
international journal of cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.475
H-Index - 234
eISSN - 1097-0215
pISSN - 0020-7136
DOI - 10.1002/(sici)1097-0215(19980302)75:5<757::aid-ijc15>3.0.co;2-3
Subject(s) - mesothelioma , doxorubicin , multidrug resistance associated proteins , cell culture , cancer research , biology , gene , multiple drug resistance , p glycoprotein , microbiology and biotechnology , gene expression , drug resistance , chemotherapy , pathology , medicine , genetics , atp binding cassette transporter , transporter
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. Int. J. Cancer 75:757–761, 1998.© 1998 Wiley‐Liss, Inc.