Sterenczak Katharina A, Willenbrock Saskia, Barann Matthias, Klemke Markus, Soller Jan T, Eberle Nina, Nolte Ingo, Bullerdiek Jörn, Murua Escobar Hugo
Small Animal Clinic and Research Cluster of Excellence REBIRTH, University of Veterinary Medicine, Bischofsholer Damm 15, D-30173 Hannover, Germany.
Gene. 2009 Apr 1;434(1-2):35-42. doi: 10.1016/j.gene.2008.10.027. Epub 2008 Nov 12.
RAGE is a member of the immunoglobulin superfamily of cell surface molecules playing key roles in pathophysiological processes, e.g. immune/inflammatory disorders, Alzheimer's disease, diabetic arteriosclerosis and tumourigenesis. In humans 19 naturally occurring RAGE splicing variants resulting in either N-terminally or C-terminally truncated proteins were identified and are lately discussed as mechanisms for receptor regulation. Accordingly, deregulation of sRAGE levels has been associated with several diseases e.g. Alzheimer's disease, Type 1 diabetes, and rheumatoid arthritis. Administration of recombinant sRAGE to animal models of cancer blocked tumour growth successfully. In spite of its obvious relationship to cancer and metastasis data focusing sRAGE deregulation and tumours is rare. In this study we screened a set of tumours, healthy tissues and various cancer cell lines for RAGE splicing variants and analysed their structure. Additionally, we analysed the ratio of the mainly found transcript variants using quantitative Real-Time PCR. In total we characterised 24 previously not described canine and 4 human RAGE splicing variants, analysed their structure, classified their characteristics, and derived their respective protein forms. Interestingly, the healthy and the neoplastic tissue samples showed in majority RAGE transcripts coding for the complete receptor and transcripts showing insertions of intron 1.
RAGE是细胞表面分子免疫球蛋白超家族的成员，在病理生理过程中发挥关键作用，如免疫/炎症性疾病、阿尔茨海默病、糖尿病性动脉硬化和肿瘤发生。在人类中，已鉴定出19种天然存在的RAGE剪接变体，这些变体导致N端或C端截短的蛋白质，最近被作为受体调节机制进行讨论。因此，可溶性RAGE（sRAGE）水平的失调与多种疾病相关，如阿尔茨海默病、1型糖尿病和类风湿性关节炎。将重组sRAGE给予癌症动物模型可成功阻断肿瘤生长。尽管sRAGE失调与癌症和转移之间存在明显关联，但聚焦sRAGE失调与肿瘤的相关数据却很少见。在本研究中，我们筛选了一组肿瘤、健康组织和各种癌细胞系中的RAGE剪接变体，并分析了它们的结构。此外，我们使用定量实时PCR分析了主要发现的转录变体的比例。我们总共鉴定了24种先前未描述的犬类RAGE剪接变体和4种人类RAGE剪接变体，分析了它们的结构，分类了它们的特征，并推导了它们各自的蛋白质形式。有趣的是，健康组织和肿瘤组织样本中大多数RAGE转录本编码完整受体，以及显示内含子1插入的转录本。
