Mapping ATP-binding cassette transporter gene expression profiles in melanocytes and melanoma cells.
ATP-binding cassette (ABC) transporters regulate the transport of a variety of physiologic substrates. Moreover, several human ABC proteins are responsible for drug exclusion in compound-treated tumor cells, providing cellular mechanisms for the development of multidrug resistance and, therefore, playing an important role in malignant transformation. As only limited information exists on the role of ABC transporters in melanoma, the aim of the study was to generate a complete expression profile of ABC transporters in this tumor entity. Using a TaqMan low-density array for 47 human ABC transporters, mRNA expression analysis was performed from normal human epidermal melanocytes (NHEM P2 and NHEM P3), nine different cell lines originating from primary melanoma (Mel Ei, Mel Juso, Mel Ho and Mel Wei), and metastases of malignant melanoma (Mel Im, Mel Ju, SK Mel 28, HTZ 19 and HMB2). Cell line-specific expression levels were compared with gene expression in pooled RNA from a variety of other human tissues. High expression levels were detected in pooled tissue RNA as well as in cells of melanocytic origin for ABCA5, ABCB2, ABCB6, ABCD3, ABCD4, ABCF1, ABCF2 and ABCF3, whereas ABCB5 revealed a melanocyte-specific high transcript level. In relation to normal melanocytes, ABCB3, ABCB6, ABCC2, ABCC4, ABCE1 and ABCF2 were significantly increased in melanoma cell lines, whereas ABCA7, ABCA12, ABCB2, ABCB4, ABCB5 and ABCD1 showed lower expression levels. In summary, we present here for the first time an ABC-transporter mRNA expression profile in melanoma in comparison to normal melanocytes. The differentially regulated ABC transporters detected by our approach may be candidate genes involved in melanoma tumorigenesis, progression and therapy resistance and could therefore be of great importance to identify novel options for melanoma therapy.
Heimerl
Susanne
S
Institute of Clinical Chemistry, University of Regensburg, Regensburg, Germany.
Bosserhoff
Anja K
AK
Langmann
Thomas
T
Ecker
Josef
J
Schmitz
Gerd
G
D018528:ATP-Binding Cassette Transporters / Q000235:genetics*; D014408:Biomarkers, Tumor / Q000235:genetics*; D002478:Cells, Cultured; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic / Q000502:physiology*; D006801:Humans; D008544:Melanocytes / Q000378:metabolism*; D008545:Melanoma / Q000235:genetics*; D000089762:Multidrug Resistance-Associated Protein 2; D020411:Oligonucleotide Array Sequence Analysis; D012333:RNA, Messenger / Q000378:metabolism; D012878:Skin Neoplasms / Q000235:genetics / Q000378:metabolism*
C000715087:ABCC2 protein, human; D018528:ATP-Binding Cassette Transporters; D014408:Biomarkers, Tumor; D000089762:Multidrug Resistance-Associated Protein 2; D012333:RNA, Messenger