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首页> 外文期刊>Pigment cell research >Principal expression of two mRNA isoforms (ABCB5 alpha and ABCB5 beta) of the ATP-binding cassette transporter gene ABCB5 in melanoma cells and melanocytes
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Principal expression of two mRNA isoforms (ABCB5 alpha and ABCB5 beta) of the ATP-binding cassette transporter gene ABCB5 in melanoma cells and melanocytes

机译：ATP结合盒转运蛋白基因ABCB5的两个mRNA亚型（ABCB5 alpha和ABCB5 beta）在黑素瘤细胞和黑素细胞中的主要表达

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摘要

ATP-binding cassette (ABC) transporters play a pivotal role in physiology and pathology. We identified and cloned two novel mRNA isoforms (ABCB 5 alpha and ABCB 5 beta) of the ABC transporter ABCB 5 in human melanoma cells. The deduced ABCB 5 alpha protein appears to be an altered splice variant containing only a putative ABC, whereas the ABCB 5 beta 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 5 alpha/beta. We found that the melanomas included among the NCI-60 panel of cell lines preferentially expressed both ABCB 5 alpha and ABCB 5 beta. However, ABCB 5 alpha/beta expression was undetectable in two amelanotic melanomas (M14 and LOX-IMVI). The expression profile of ABCB 5 alpha/beta in all of the other melanomas of the panel was confirmed both by RT-PCR and by sequencing. Neither ABCB 5 alpha nor ABCB 5 beta expression was found in normal tissues such as liver, spleen, thymus, kidney, lung, colon, small intestines or placenta. ABCB 5 alpha/beta mRNAs were also expressed in normal melanocytes and in retinal pigment epithelial cells, suggesting that ABCB 5 alpha/beta expression is pigment cell-specific and might be involved in melanogenesis. Our findings indicate that expression of ABCB 5 alpha/beta might possibly provide two novel molecular markers for differential diagnosis of melanomas and constitute potential molecular targets for therapy of melanomas.
机译：ATP结合盒（ABC）转运蛋白在生理和病理学中起着关键作用。我们鉴定并克隆了人类黑素瘤细胞中ABC转运蛋白ABCB 5的两个新的mRNA亚型（ABCB 5 alpha和ABCB 5 beta）。推导的ABCB 5α蛋白似乎是一个仅包含推定的ABC的可变剪接变体，而ABCB 5 beta同工型与ABCB1（MDR1）具有大约70％的相似性，并且推导的拓扑结构类似于整个羧基末端一半包括完整的ABC的ABCB1基因产物P-糖蛋白。使用RNA印迹，实时PCR和常规RT-PCR来验证ABCB5α/β的表达谱。我们发现，包括在细胞系的NCI-60组中的黑色素瘤优先表达了ABCB 5 alpha和ABCB 5 beta。但是，在两个釉质黑色素瘤（M14和LOX-IMVI）中均未检测到ABCB 5 alpha / beta表达。通过RT-PCR和测序均证实了ABCB5α/β在该组所有其他黑色素瘤中的表达谱。在正常组织如肝，脾，胸腺，肾脏，肺，结肠，小肠或胎盘中均未发现ABCB 5 alpha和ABCB 5 beta表达。 ABCB 5 alpha / beta mRNAs在正常黑素细胞和视网膜色素上皮细胞中也表达，这表明ABCB 5 alpha / beta表达是色素细胞特异性的，可能与黑色素生成有关。我们的发现表明，ABCB 5 alpha / beta的表达可能为黑色素瘤的鉴别诊断提供了两个新颖的分子标记，并构成了治疗黑色素瘤的潜在分子靶标。

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