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外分泌性胰腺癌中过表达的人Rab20的特征分析

Characterization of human Rab20 overexpressed in exocrine pancreatic carcinoma.

作者信息

Amillet Jean-Michel, Ferbus Didier, Real Francisco X, Antony Claude, Muleris Martine, Gress Thomas M, Goubin Gérard

机构信息

FRE 2584 CNRS, Institut Curie, 26 rue d'Ulm, 75248 Paris Cedex 05, France.

出版信息

Hum Pathol. 2006 Mar;37(3):256-63. doi: 10.1016/j.humpath.2005.10.017.

Abstract

In a large-scale analysis of gene expression in pancreatic cancer, we isolated the homologue of the mouse Rab20. The mouse protein was previously identified during a search for novel Rab proteins, a family of small GTP-binding proteins involved in the regulation of intracellular vesicular transport. The Rab20 protein has no close relationship to any member of the Rab protein subfamily. In contrast to other members, it contains an insertion of 40 amino acids of unknown function and an inversion of 3 amino acids at the position corresponding to codon 61 in p21ras proteins. Using immunofluorescence and immunoelectron microscopy, we localized the Rab20 protein in the vicinity of the Golgi apparatus. Rab20 expression was detected by Western blot analysis in 11 of 11 pancreatic tumor cell lines and 7 of 8 primary pancreatic carcinomas. Absent or very faint expression was observed in normal pancreas cell extracts. Immunohistochemical analysis of Rab20 in tissues showed low or absent expression in normal pancreas and stronger expression in 15 of 18 exocrine pancreatic adenocarcinomas. Rab20 was also detected in preneoplastic pancreatic intraductal neoplasia lesions, suggesting that its up-regulation may be an early event in pancreatic carcinogenesis.

摘要

在一项对胰腺癌基因表达的大规模分析中,我们分离出了小鼠Rab20的同源物。该小鼠蛋白先前是在寻找新型Rab蛋白的过程中被鉴定出来的,Rab蛋白是一类参与细胞内囊泡运输调控的小GTP结合蛋白家族。Rab蛋白家族的任何成员与Rab20蛋白都没有密切关系。与其他成员不同的是,它含有一段功能未知的40个氨基酸的插入序列,并且在对应于p21ras蛋白中第61位密码子的位置有3个氨基酸的倒位。我们利用免疫荧光和免疫电子显微镜技术,将Rab20蛋白定位在高尔基体附近。通过蛋白质免疫印迹分析,在11种胰腺肿瘤细胞系中的11种以及8例原发性胰腺癌中的7例中检测到了Rab20的表达。在正常胰腺细胞提取物中未观察到或仅观察到非常微弱的表达。对组织中Rab20进行免疫组织化学分析显示,正常胰腺中Rab20表达较低或无表达,而在18例胰腺外分泌腺癌中的15例中表达较强。在胰腺导管内瘤变的肿瘤前病变中也检测到了Rab20,这表明其上调可能是胰腺癌发生过程中的一个早期事件。

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