Principal expression of two mRNA isoforms (ABCB5α and ABCB5β) of the ATP-binding cassette transporter gene ABCB5 in melanoma cells and melanocytes

ATP-binding cassette (ABC) transporters play a pivotal role in physiology and pathology. We identified and cloned two novel mRNA isoforms (ABCB5α and ABCB5β) of the ABC transporter ABCB5 in human melanoma cells. The deduced ABCB5α protein appears to be an altered splice variant containing only a putative ABC, whereas the ABCB5β isoform shares approximately 70% similarity with ABCB1 (MDR1) and has a deduced topological arrangement similar to that of the whole carboxyl terminal half of the ABCB1 gene product, P-glycoprotein, including an intact ABC. Northern blot, real-time PCR, and conventional RT-PCR were used to verify the expression profiles of ABCB5α/β. We found that the melanomas included among the NCl-60 panel of cell lines preferentially expressed both ABCB5α and ABCB5β. However, ABCB5α/β expression was undetectable in two amelanotic melanomas (M14 and LOX-IMVI). The expression profile of ABCB5α/β in all of the other melanomas of the panel was confirmed both by RT-PCR and by sequencing. Neither ABCB5α nor ABCB5β expression was found in normal tissues such as liver, spleen, thymus, kidney, lung, colon, small intestines or placenta. ABCB5α/β mRNAs were also expressed in normal melanocytes and in retinal pigment epithelial cells, suggesting that ABCB5α/β expression is pigment cell-specific and might be involved in melanogenesis. Our findings indicate that expression of ABCB5α/β might possibly provide two novel molecular markers for differential diagnosis of melanomas and constitute potential molecular targets for therapy of melanomas.