Disseminated malignant melanoma is characterized by unresponsiveness to chemotherapy without overexpressing corresponding P-glycoprotein. Another ABC-transporter protein functioning as transmembrane drug-efflux pump and involved in multidrug resistance (MDR), is the multidrug resistance-associated protein (MRP). We investigated wether MRP plays a role in malignant melanoma chemoresistance. Using the RT-PCR (two different oligonucleotid primer sets) we determined mRNA-expression in 33 cell lines established from primary tumors (n=11), metastatic lesions (n=17) and malignant effusions (n=5). Protein expression was determined by Western blot analysis (MRPm6, QCRL-1) and confirmed by immunocytochemistry. All cell lines scored positiv for MRP mRNA at different levels (5high, 13 intermediate, 15low). Levels of MRP mRNA were significantly higher in primary tumors as compared to metastases and malignant effusions. The respective protein was detectable in Western blot and in immunocytochemistry. Accumulation studies using <sup>3</sup>H-daunomycin as MRP substrate and genistein as specific MRP modulator were perfornled and revealed - in contrast to the control cell models GLC4/ADR and HL601/AR - no drug efflux activily of MRP. In conclusion melanoma cell lines express MRP mRNA and protein at different levels. The biological role has to be investigated in further studies.
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