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Chemotherapy induces or increases expression of multidrug resistance-associated protein in malignant melanoma cells

Chemotherapy induces or increases expression of multidrug resistance-associated protein in malignant melanoma cells

British Journal of Dermatology 144(4): 745-750, April

Background: Human malignant melanoma is notoriously resistant to chemotherapeutic agents. Melanoma-derived cell lines are often markedly chemoresistant, suggesting that cellular mechanisms mediate generation of the multidrug resistance (MDR) phenotype. This phenotype is often due to P-glycoprotein (Pgp) and the MDR-associated protein (MRP), which are drug transporter proteins associated with resistance to a broad spectrum of lipophilic drugs. Objectives: To determine the relationships between the expression of the MDR gene MDR-1 (the product of which is Pgp) or the MRP gene, and clinical chemoresistance of malignant melanoma. Methods: We examined changes in the expression of MDR-1 and MRP genes at the mRNA level before and after chemotherapy by reverse transcription-polymerase chain reaction (RT-PCR) analysis using formalin-fixed, paraffin-embedded sections of 18 specimens taken from eight melanoma patients. mRNA expression of the MDR-1 and MRP gene-specific PCR products was quantitatively determined by densitometry and compared with that of an internal standard (beta-actin). Results: Five of seven primary melanomas were found to express the MRP gene to a certain extent even before chemotherapy. After first and second courses of chemotherapy, six patients had an increased ratio of MRP mRNA to beta-actin mRNA compared with the prechemotherapy levels in the same patients. None of the cases of melanoma expressed MDR-1. Conclusions: These results suggest that a significant mRNA level of MRP gene was intrinsically present in malignant melanoma even before exposure to chemotherapeutic drugs and increased in its expression after chemotherapy, suggesting that MRP plays a part in increasing the chemoresistance of malignant melanoma during chemotherapy.

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Accession: 010314276

Download citation: RISBibTeXText

PMID: 11298532

DOI: 10.1046/j.1365-2133.2001.04129.x

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