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Syntaxin-7蛋白在良性黑素细胞和恶性黑色素瘤中的选择性表达。

Selective expression of Syntaxin-7 protein in benign melanocytes and malignant melanoma.

作者信息

Strömberg Sara, Agnarsdóttir Margrét, Magnusson Kristina, Rexhepaj Elton, Bolander Asa, Lundberg Emma, Asplund Anna, Ryan Denise, Rafferty Mairin, Gallagher William M, Uhlen Mathias, Bergqvist Michael, Ponten Fredrik

机构信息

Department of Genetics and Pathology, Rudbeck Laboratory, Uppsala University, SE-75185 Uppsala, Sweden.

出版信息

J Proteome Res. 2009 Apr;8(4):1639-46. doi: 10.1021/pr800745e.

Abstract

To search for proteins expressed in human melanocytes and melanoma, we employed an antibody-based proteomics strategy to screen for protein expression in tissue microarrays containing normal tissues, cancer tissues and cell lines. Syntaxin-7 (STX7) was identified as a novel protein, not previously characterized in cells of melanocytic lineage, displaying a cell type-specific protein expression pattern. In tumor tissues, STX7 was expressed in malignant melanoma and lymphoma. The protein was further characterized regarding subcellular localization, specificity, tissue distribution pattern and potential as a diagnostic and prognostic marker using cell lines and tissue microarrays containing normal skin, melanocytic nevi and primary and metastatic melanoma. STX7 was expressed in normal melanocytes, various benign melanocytic nevi, atypical nevi and malignant melanoma. Analysis in two independent melanoma cohorts demonstrated STX7 expression in nearly all investigated tumors, although at varying levels (> 90% positive tumors). The expression level of STX7 protein was inversely correlated to tumor stage, suggesting that decreased expression of STX7 is associated with more aggressive tumors. In conclusion, we present protein profiling data for a novel protein showing high sensitivity and specificity for cells of the melanocytic lineage. The presented antibody-based proteomics approach can be used as an effective strategy to identify novel tumor markers and evaluate their potential clinical relevance.

摘要

为了寻找在人类黑素细胞和黑色素瘤中表达的蛋白质,我们采用了基于抗体的蛋白质组学策略,以筛选包含正常组织、癌组织和细胞系的组织微阵列中的蛋白质表达。Syntaxin-7(STX7)被鉴定为一种新蛋白,此前在黑素细胞系细胞中尚未有特征描述,它呈现出细胞类型特异性的蛋白质表达模式。在肿瘤组织中,STX7在恶性黑色素瘤和淋巴瘤中表达。利用包含正常皮肤、黑素细胞痣以及原发性和转移性黑色素瘤的细胞系和组织微阵列,进一步对该蛋白的亚细胞定位、特异性、组织分布模式以及作为诊断和预后标志物的潜力进行了表征。STX7在正常黑素细胞、各种良性黑素细胞痣、非典型痣和恶性黑色素瘤中均有表达。对两个独立的黑色素瘤队列的分析表明,几乎所有研究的肿瘤中都有STX7表达,尽管表达水平各不相同(>90%的肿瘤呈阳性)。STX7蛋白的表达水平与肿瘤分期呈负相关,这表明STX7表达降低与更具侵袭性的肿瘤有关。总之,我们展示了一种新蛋白的蛋白质谱数据,该蛋白对黑素细胞系细胞具有高敏感性和特异性。所提出的基于抗体的蛋白质组学方法可作为一种有效的策略来鉴定新的肿瘤标志物并评估其潜在的临床相关性。

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