Amyloid precursor-like protein 1 is differentially upregulated in neuroendocrine tumours of the gastrointestinal tract
Amyloid precursor-like protein 1 is differentially upregulated in neuroendocrine tumours of the gastrointestinal tract
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DOI：
10.1677/erc-07-0145
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发表时间：
2008-06-01
影响因子：
3.9
通讯作者：
Nilsson, Ola
中科院分区：
文献类型：
--
作者：
Arvidsson, Yvonne;Andersson, Ellinor;Nilsson, Ola
我们通过微阵列分析检测了小肠类癌的全球基因表达谱。许多基因的高表达被发现，包括淀粉样前体蛋白1(APLP1)。实时定量聚合酶链式反应和免疫印迹分析显示APLP1在类癌转移癌中的表达高于原发肿瘤，提示APLP1在肿瘤扩散中起作用。胃肠胰腺肿瘤的组织芯片分析表明，与相同部位的非神经内分泌肿瘤相比，神经内分泌(NE)肿瘤中APLP1的表达频率较高，APLP2的表达频率较低。大量胃肠道外肿瘤基因表达数据的Meta分析证实，APLP1的表达与NE表型之间存在相关性，在NE肿瘤中，APLP1的高表达伴随着APLP2的下调。在共聚焦显微镜下，APLP1、APLP2和淀粉样前体蛋白(APP)在类癌细胞(GOT1)中的细胞定位显示与突触素部分共定位。这表明APP家族蛋白通过突触微泡运输到细胞膜，它们可能影响转归细胞的粘附性和侵袭性。我们的结论是，APLP1在胃肠道NE肿瘤中差异表达，APLP1可能在小肠类癌的扩散中起重要作用。在NE肿瘤中发现APLP1为治疗提供了一个新的靶点，也可以作为肿瘤特异性标志物。
We have examined the global gene expression profile of small intestinal carcinoids by microarray analysis. High expression of a number of genes was found including amyloid precursor-like protein 1 (APLP1). Quantitative real-time PCR and western blot analysis demonstrated higher expression of APLP1 in carcinoid metastases relative to primary tumours indicating a role of APLP1 in tumour dissemination. Tissue microarray analysis of gastroentero-pancreatic tumours demonstrated a high frequency of APLP1 expression and a low frequency of APLP2 expression in neuroendocrine (NE) tumours when compared with non-NE tumours at the same sites. Meta-analysis of gene expression data from a large number of tumours outside the gastrointestinal tract confirmed acorrelation between APLP1 expression and NE phenotype where high expression of APLP1 was accompanied by downregulation of APLP2 in NE tumours. Cellular localization of APLP1, APLP2 and amyloid precursor protein (APP) in carcinoid cells (GOT1) by confocal microscopy demonstrated partial co-localization with synaptophysin. This suggests that the APP family of proteins is transported to the cell membrane by synaptic microvesicles and that they may influence turnout cell adhesion and invasiveness. We conclude that APLP1 is differentially upregulated in gastrointestinal NE tumours and that APLP1 may be important for the dissemination of small intestinal carcinoids. Identification of APLP1 in NE tumours offers a novel target for treatment and may also serve as a tumour-specific marker.