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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.

作者信息

Ogretmen B, Bahadori H R, McCauley M D, Boylan A, Green M R, Safa A R

机构信息

Department of Experimental Oncology, Medical University of South Carolina, Charleston 29425, USA.

出版信息

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.

DOI:10.1002/(sici)1097-0215(19980302)75:5<757::aid-ijc15>3.0.co;2-3
PMID:9495245
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.

摘要

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