title: 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.
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.
authors.affiliation: Department of Experimental Oncology, Medical University of South Carolina, Charleston 29425, USA.
authors.forename: B
authors.initials: B
authors.lastname: Ogretmen
authors.forename: H R
authors.initials: HR
authors.lastname: Bahadori
authors.forename: M D
authors.initials: MD
authors.lastname: McCauley
authors.forename: A
authors.initials: A
authors.lastname: Boylan
authors.forename: M R
authors.initials: MR
authors.lastname: Green
authors.forename: A R
authors.initials: AR
authors.lastname: Safa
mesh_terms: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000235:genetics*; D018528:ATP-Binding Cassette Transporters / Q000235:genetics*; D004317:Doxorubicin / Q000494:pharmacology*; D019008:Drug Resistance, Neoplasm; D004848:Epithelium / Q000378:metabolism; D015870:Gene Expression; D005721:Glutamate-Cysteine Ligase / Q000235:genetics*; D006801:Humans; D008654:Mesothelioma / Q000188:drug therapy / Q000201:enzymology / Q000378:metabolism*; D027425:ATP-Binding Cassette, Sub-Family C Proteins; D012333:RNA, Messenger / Q000235:genetics; D012334:RNA, Neoplasm / Q000235:genetics; D014407:Tumor Cells, Cultured
chemical_list: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D018528:ATP-Binding Cassette Transporters; D004317:Doxorubicin; D005721:Glutamate-Cysteine Ligase; D027425:ATP-Binding Cassette, Sub-Family C Proteins; D012333:RNA, Messenger; D012334:RNA, Neoplasm