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ATP-binding cassette (ABC) transporters play a pivotal role in physiology and pathology. We identified and cloned two novel mRNA isoforms (ABCB 5α andABCB 5β) of the ABC transporterABCB 5 in human melanoma cells. The deducedABCB 5α protein appears to be an altered splice variant containing only a putative ABC, whereas theABCB 5β isoform shares approximately 70% similarity withABCB1 (MDR1) and has a deduced topological arrangement similar to that of the whole carboxyl terminal half of theABCB1 gene product, P-glycoprotein, including an intact ABC. Northern blot, real-time PCR, and conventional RT-PCR were used to verify the expression profiles ofABCB 5α/β. We found that the melanomas included among the NCI-60 panel of cell lines preferentially expressed bothABCB 5α andABCB 5β. However,ABCB 5α/β expression was undetectable in two amelanotic melanomas (M14 and LOX-IMVI). The expression profile ofABCB 5α/β in all of the other melanomas of the panel was confirmed both by RT-PCR and by sequencing. NeitherABCB 5α norABCB 5β expression was found in normal tissues such as liver, spleen, thymus, kidney, lung, colon, small intestines or placenta.ABCB 5α/β mRNAs were also expressed in normal melanocytes and in retinal pigment epithelial cells, suggesting thatABCB 5α/β expression is pigment cell-specific and might be involved in melanogenesis. Our findings indicate that expression ofABCB 5α/β might possibly provide two novel molecular markers for differential diagnosis of melanomas and constitute potential molecular targets for therapy of melanomas. [ABSTRACT FROM AUTHOR]