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
✍ Scribed by Besim Ogretmen; Hamid R. Bahadori; Mary D. McCauley; Alice Boylan; Mark R. Green; Ahmad R. Safa
- Publisher
- John Wiley and Sons
- Year
- 1998
- Tongue
- French
- Weight
- 84 KB
- Volume
- 75
- Category
- Article
- ISSN
- 0020-7136
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✦ Synopsis
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 resistanceassociated protein (MRP) and ␥-glutamylcysteine synthetase (␥-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 ␥-GCS h in chemoresistance in mesotheliomas.