Characterization of human Rab20 overexpressed in exocrine pancreatic carcinoma

Characterization of human Rab20 overexpressed in exocrine pancreatic carcinoma
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DOI:
10.1016/j.humpath.2005.10.017
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发表时间:
2006-03-01
期刊:
影响因子:
3.3
通讯作者:
Goubin, G
Goubin, G
中科院分区:
医学3区
文献类型:
--
作者:
Amillet, JM;Ferbus, D;Goubin, G

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在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。该小鼠蛋白之前是在寻找新型 Rab 蛋白时发现的,Rab 蛋白是参与细胞内囊泡运输调节的小型 GTP 结合蛋白家族。 Rab20 蛋白与 Rab 蛋白亚家族的任何成员都没有密切关系。与其他成员相比,它包含 40 个功能未知的氨基酸的插入,以及在对应于 p21ras 蛋白中密码子 61 的位置处的 3 个氨基酸的倒置。使用免疫荧光和免疫电子显微镜,我们将 Rab20 蛋白定位在高尔基体附近。通过蛋白质印迹分析,在 11 种胰腺肿瘤细胞系中的 11 种和 8 种原发性胰腺癌中的 7 种中检测到 Rab20 表达。在正常胰腺细胞提取物中观察到不存在或非常微弱的表达。组织中 Rab20 的免疫组织化学分析显示,在正常胰腺中表达较低或不表达,在 18 例外分泌胰腺腺癌中的 15 例中表达较强。 Rab20也在癌前胰腺导管内肿瘤病变中检测到,表明其上调可能是胰腺癌发生的早期事件。 (c) 2006 Elsevier Inc. 保留所有权利。
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. (c) 2006 Elsevier Inc. All rights reserved.