Mapping ATP-binding cassette transporter gene expression profiles in melanocytes and melanoma cells
Mapping ATP-binding cassette transporter gene expression profiles in melanocytes and melanoma cells
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DOI：
10.1097/cmr.0b013e3282a7e0b9
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发表时间：
2007-10-01
影响因子：
2.2
通讯作者：
Schmitz, Gerd
中科院分区：
文献类型：
--
作者：
Helmerl, Susanne;Bosserhoff, Anja K.;Schmitz, Gerd
atp结合盒（ABC）转运体调节多种生理底物的转运。此外，几种人类ABC蛋白在化合物处理的肿瘤细胞中负责药物排斥，为多药耐药的发展提供细胞机制，因此在恶性转化中发挥重要作用。由于关于ABC转运蛋白在黑色素瘤中的作用的信息有限，本研究的目的是生成ABC转运蛋白在该肿瘤实体中的完整表达谱。利用TaqMan低密度阵列对47个人类ABC转运蛋白进行mRNA表达分析，分析了正常人类表皮黑色素细胞（nhemp2和nhem133）、9种不同的原发黑色素瘤细胞系（Mel Ei、Mel Juso、Mel Ho和Mel Wei）以及恶性黑色素瘤转移细胞系（Mel Im、Mel Ju、SK Mel 28、htz19和HMB2）的mRNA表达情况。细胞系特异性表达水平与来自多种其他人体组织的聚合RNA中的基因表达水平进行了比较。ABCA5、ABCB2、ABCB6、ABCD3、ABCD4、ABCF1、ABCF2和ABCF3在汇集的组织RNA和黑色素细胞起源细胞中均有高水平表达，而ABCB5在黑色素细胞特异性高水平转录。与正常黑色素细胞相比，ABCB3、ABCB6、ABCC2、ABCC4、ABCE1和ABCF2在黑色素瘤细胞系中表达水平显著升高，而ABCA7、ABCA112、ABCB2、ABCB4、ABCB5和ABCD1表达水平较低。总之，我们在这里首次提出了与正常黑色素细胞相比，黑色素瘤中abc转运蛋白mRNA的表达谱。通过我们的方法检测到的差异调节的ABC转运蛋白可能是参与黑色素瘤发生、进展和治疗耐药性的候选基因，因此可能对确定黑色素瘤治疗的新选择非常重要。
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 133), 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, ABCA112, 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.