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高迁移率族蛋白A2表达水平升高与胰腺外分泌组织的恶性表型相关。

An increased high-mobility group A2 expression level is associated with malignant phenotype in pancreatic exocrine tissue.

作者信息

Abe N, Watanabe T, Suzuki Y, Matsumoto N, Masaki T, Mori T, Sugiyama M, Chiappetta G, Fusco A, Atomi Y

机构信息

First Department of Surgery, Kyorin University School of Medicine, 6-20-2, Shinkawa, Mitaka, Tokyo 181-8611, Japan.

出版信息

Br J Cancer. 2003 Dec 1;89(11):2104-9. doi: 10.1038/sj.bjc.6601391.

Abstract

The altered form of the high-mobility group A2 (HMGA2) gene is somehow related to the generation of human benign and malignant tumours of mesenchymal origin. However, only a few data on the expression of HMGA2 in malignant tumour originating from epithelial tissue are available. In this study, we examined the HMGA2 expression level in pancreatic carcinoma, and investigated whether alterations in the HMGA2 expression level are associated with a malignant phenotype in pancreatic tissue. High-mobility group A2 mRNA and protein expression was determined in eight surgically resected specimens of non-neoplastic tissue (six specimens of normal pancreatic tissue and two of chronic pancreatitis tissue) and 27 pancreatic carcinomas by highly sensitive reverse transcriptase-polymerase chain reaction (RT-PCR) techniques and immunohistochemical staining, respectively. Reverse transcriptase-polymerase chain reaction analysis revealed the expression of the HMGA2 gene in non-neoplastic pancreatic tissue, although its expression level was significantly lower than that in carcinoma. Immunohistochemical analysis indicated that the presence of the HMGA2 gene in non-neoplastic pancreatic tissue observed in RT-PCR reflects its abundant expression in islet cells, together with its focal expression in duct epithelial cells. Intense and multifocal or diffuse HMGA2 immunoreactivity was noted in all the pancreatic carcinoma examined. A strong correlation between HMGA2 overexpression and the diagnosis of carcinoma was statistically verified. Based on these findings, we propose that an increased expression level of the HMGA2 protein is closely associated with the malignant phenotype in the pancreatic exocrine system, and accordingly, HMGA2 could serve as a potential diagnostic molecular marker for distinguishing pancreatic malignant cells from non-neoplastic pancreatic exocrine cells.

摘要

高迁移率族蛋白A2(HMGA2)基因的变异形式与人类间充质来源的良性和恶性肿瘤的发生在某种程度上相关。然而,关于HMGA2在上皮组织来源的恶性肿瘤中的表达数据却很少。在本研究中,我们检测了胰腺癌中HMGA2的表达水平,并研究了HMGA2表达水平的改变是否与胰腺组织的恶性表型相关。分别采用高灵敏度逆转录聚合酶链反应(RT-PCR)技术和免疫组化染色,检测了8例手术切除的非肿瘤组织标本(6例正常胰腺组织标本和2例慢性胰腺炎组织标本)和27例胰腺癌组织中高迁移率族蛋白A2 mRNA和蛋白的表达。逆转录聚合酶链反应分析显示HMGA2基因在非肿瘤性胰腺组织中有表达,但其表达水平显著低于癌组织。免疫组化分析表明,RT-PCR检测到的非肿瘤性胰腺组织中HMGA2基因的存在反映了其在胰岛细胞中的丰富表达,以及在导管上皮细胞中的局灶性表达。在所有检测的胰腺癌中均观察到强烈的多灶性或弥漫性HMGA2免疫反应性。经统计学验证,HMGA2过表达与癌的诊断之间存在强相关性。基于这些发现,我们提出HMGA2蛋白表达水平的升高与胰腺外分泌系统的恶性表型密切相关,因此,HMGA2可作为区分胰腺恶性细胞与非肿瘤性胰腺外分泌细胞的潜在诊断分子标志物。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5823/2376847/35adcd8d5c65/89-6601391f1.jpg

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