Overexpression of multidrug resistance-associated protein (MRP) increases resistance to natural product drugs

Amplification of the gene encoding multidrug resistance-associated protein (MRP) and overexpression of its cognate mRNA have been detected in multidrug-resistant cell lines derived from several different tumor types. To establish whether or not the increase in MRP is responsible for drug resistance...

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Bibliographic Details
Published in:Cancer research (Chicago, Ill.) Ill.), 1994-01, Vol.54 (2), p.357-361
Main Authors: GRANT, C. E, GUNNAR VLADIMARSSON, HIPFNER, D. R, ALMQUIST, K. C, COLE, S. P. C, DEELEY, R. G
Format: Article
Language:English
Subjects:
Antineoplastic agents
Biological and medical sciences
Carcinoma, Small Cell - genetics
Carcinoma, Small Cell - metabolism
Doxorubicin - pharmacology
Drug Resistance - genetics
Drug Resistance - physiology
Gene Amplification - genetics
General aspects
HeLa Cells
Humans
Lung Neoplasms - genetics
Lung Neoplasms - metabolism
Medical sciences
Neoplasm Proteins - chemistry
Neoplasm Proteins - genetics
Pharmacology. Drug treatments
Phenotype
RNA, Messenger - analysis
RNA, Neoplasm - analysis
Transfection
Tumor Cells, Cultured
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Summary:Amplification of the gene encoding multidrug resistance-associated protein (MRP) and overexpression of its cognate mRNA have been detected in multidrug-resistant cell lines derived from several different tumor types. To establish whether or not the increase in MRP is responsible for drug resistance in these cell lines, we have transfected HeLa cells with MRP expression vectors. The transfectants display an increase in resistance to doxorubicin that is proportional to the levels of a M(r) 190,000, integral membrane protein recognized by anti-MRP antibodies. The transfectants are also resistant to vincristine and VP-16 but not to cisplatin. The results demonstrate that MRP overexpression confers a multidrug resistance phenotype similar to that formerly associated exclusively with elevated levels of P-glycoprotein.
ISSN:0008-5472
1538-7445