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Chemotherapy induces or increases expression of multidrug resistance‐associated protein in malignant melanoma cells
Author(s) -
Ichihashi N.,
Kitajima Y.
Publication year - 2001
Publication title -
british journal of dermatology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.304
H-Index - 179
eISSN - 1365-2133
pISSN - 0007-0963
DOI - 10.1046/j.1365-2133.2001.04129.x
Subject(s) - melanoma , multiple drug resistance , chemotherapy , gene expression , biology , cancer research , p glycoprotein , drug resistance , gene , reverse transcription polymerase chain reaction , messenger rna , multidrug resistance associated proteins , doxorubicin , phenotype , microbiology and biotechnology , atp binding cassette transporter , transporter , genetics
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 (β‐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 β‐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.