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

N Ichihashi1, Y Kitajima

  • 1Department of Dermatology, Gifu University School of Medicine, 40 Tukasa-machi, Gifu City 500-8705, Japan. ichihasi@cc.gifu-u.ac.jp

The British Journal of Dermatology
|April 12, 2001
PubMed
Abstract

Insights

The multidrug resistance-associated protein (MRP) gene is intrinsically present in malignant melanoma and its expression increases after chemotherapy. This suggests MRP contributes to chemoresistance in melanoma patients.

Area of Science:

  • Oncology
  • Molecular Biology
  • Pharmacology

Background:

  • Human malignant melanoma exhibits significant resistance to chemotherapy.
  • This chemoresistance is often linked to the multidrug resistance (MDR) phenotype, mediated by drug transporter proteins like P-glycoprotein (Pgp) and the MDR-associated protein (MRP).

Purpose of the Study:

  • To investigate the relationship between the expression of the MDR-1 gene (encoding Pgp) or the MRP gene and clinical chemoresistance in malignant melanoma.
  • To understand the role of these genes in the development of drug resistance in melanoma.

Main Methods:

  • Examined changes in MDR-1 and MRP gene expression at the mRNA level using reverse transcription-polymerase chain reaction (RT-PCR).
  • Analyzed formalin-fixed, paraffin-embedded tissue from 18 melanoma specimens (eight patients) before and after chemotherapy.
  • Quantitatively determined mRNA expression by densitometry, comparing gene-specific products to an internal standard (beta-actin).

Main Results:

  • The MRP gene was expressed in five of seven primary melanomas prior to chemotherapy.
  • Following chemotherapy, six patients showed increased MRP mRNA levels compared to pre-chemotherapy levels.
  • The MDR-1 gene was not expressed in any of the melanoma cases studied.

Conclusions:

  • A significant baseline level of MRP gene mRNA is present in malignant melanoma before chemotherapy exposure.
  • MRP gene expression increases following chemotherapy, indicating its role in enhancing chemoresistance.
  • MRP appears to be a key factor in the development of chemotherapy resistance in malignant melanoma.

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