Principal expression of two mRNA isoforms (ABCB 5alpha and ABCB 5beta ) of the ATP-binding cassette transporter gene ABCB 5 in melanoma cells and melanocytes.

Abstract

ATP-binding cassette (ABC) transporters play a pivotal role in physiology and pathology. We identified and cloned two novel mRNA isoforms (ABCB 5alpha and ABCB 5beta) of the ABC transporter ABCB 5 in human melanoma cells. The deduced ABCB 5alpha protein appears to be an altered splice variant containing only a putative ABC, whereas the ABCB 5beta 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 ABCB 5alpha/beta. We found that the melanomas included among the NCI-60 panel of cell lines preferentially expressed both ABCB 5alpha and ABCB 5beta. However, ABCB 5alpha/beta expression was undetectable in two amelanotic melanomas (M14 and LOX-IMVI). The expression profile of ABCB 5alpha/beta in all of the other melanomas of the panel was confirmed both by RT-PCR and by sequencing. Neither ABCB 5alpha nor ABCB 5beta expression was found in normal tissues such as liver, spleen, thymus, kidney, lung, colon, small intestines or placenta. ABCB 5alpha/beta mRNAs were also expressed in normal melanocytes and in retinal pigment epithelial cells, suggesting that ABCB 5alpha/beta expression is pigment cell-specific and might be involved in melanogenesis. Our findings indicate that expression of ABCB 5alpha/beta might possibly provide two novel molecular markers for differential diagnosis of melanomas and constitute potential molecular targets for therapy of melanomas.

• Authors: Kevin G Chen, Gergely Szakács, Jean-Philippe Annereau, Francois Rouzaud, Xing-Jie Liang, Julio C Valencia, Chandrasekharam N Nagineni, John J Hooks, Vincent J Hearing, Michael M Gottesman
• Journal: Pigment cell research (Pigment Cell Res) Vol. 18 Issue 2 Pg. 102-12 (Apr 2005) ISSN: 0893-5785 [Print] Denmark
• PMID: 15760339 (Publication Type: Journal Article)

Chemical References

• ABCB5 protein, human
• ATP Binding Cassette Transporter, Subfamily B
• ATP Binding Cassette Transporter, Subfamily B, Member 1
• Biomarkers, Tumor
• RNA, Messenger

Topics

• ATP Binding Cassette Transporter, Subfamily B
• ATP Binding Cassette Transporter, Subfamily B, Member 1 (biosynthesis, genetics)
• Alternative Splicing
• Amino Acid Sequence
• Base Sequence
• Biomarkers, Tumor (biosynthesis, genetics)
• Cell Line, Tumor
• Cells, Cultured
• Drug Resistance, Multiple
• Drug Resistance, Neoplasm
• Gene Expression Profiling
• Gene Library
• Humans
• Melanocytes (metabolism)
• Melanoma
• Molecular Sequence Data
• Organ Specificity
• RNA, Messenger (biosynthesis)