Abe N, Watanabe T, Masaki T, Mori T, Sugiyama M, Uchimura H, Fujioka Y, Chiappetta G, Fusco A, Atomi Y
First Department of Surgery, Kyorin University School of Medicine, Tokyo, Japan.
Cancer Res. 2000 Jun 15;60(12):3117-22.
The high mobility group I (HMGI) family of proteins in mammals belongs to a group of nonhistone nuclear proteins known as architectural transcriptional factors. They function in vivo as both structural components of chromatin and auxiliary gene transcription factors. In an earlier study (N. Abe et al, Cancer Res., 59: 1169-1174, 1999), we demonstrated that the expression level of the HMGI(Y) gene/proteins was significantly increased in colorectal adenocarcinoma and colorectal adenoma with severe cellular atypia. In the current study, we analyzed HMGI(Y) expression in several human pancreatic lesions to investigate (a) whether HMGI(Y) overexpression is also observed in pancreatic carcinoma, and (b) the role of HMGI(Y) in the diagnosis of pancreatic neoplasms. To this end, HMGI(Y) expression was determined at the protein level by immunohistochemistry using a HMGI(Y)-specific antibody in 6 surgically resected specimens of nonneoplastic tissue (4 specimens of normal pancreatic tissue and 2 specimens of chronic pancreatitis tissue), 8 pancreatic cystic neoplasms (5 intraductal papillary mucinous adenomas, 1 serous cystadenoma, and 2 solid pseudopapillary tumors), and 15 duct cell carcinomas of the pancreas. Immunohistochemical analysis revealed intense nuclear staining in the pancreatic carcinoma cells, whereas only very faint nuclear staining was seen in the nonneoplastic cells. There was a strong correlation between HMGI(Y) protein overexpression and a diagnosis of carcinoma (P = 0.000018). Thus, an increased expression level of the HMGI(Y) proteins was clearly associated with the malignant phenotype in pancreatic tissue. In addition, a low level of protein expression was also apparent in two of the cystic neoplasms that exhibited cellular atypia, but not in those that did not exhibit cellular atypia. Based on these findings, we propose that the HMGI(Y) proteins could be closely associated with tumorigenesis in the pancreas and that HMGI(Y) could serve as a potential diagnostic molecular marker for distinguishing pancreatic malignancies unambiguously from normal tissue or benign lesions.
哺乳动物中的高迁移率族I（HMGI）蛋白家族属于一组被称为结构转录因子的非组蛋白核蛋白。它们在体内既作为染色质的结构成分，又作为辅助基因转录因子发挥作用。在早期的一项研究中（N. Abe等人，《癌症研究》，59: 1169 - 1174，1999），我们证明了HMGI(Y)基因/蛋白的表达水平在结直肠癌和伴有严重细胞异型性的结肠腺瘤中显著升高。在当前的研究中，我们分析了几种人类胰腺病变中的HMGI(Y)表达情况，以研究：（a）胰腺癌中是否也观察到HMGI(Y)过表达；（b）HMGI(Y)在胰腺肿瘤诊断中的作用。为此，我们使用HMGI(Y)特异性抗体，通过免疫组织化学在蛋白质水平上测定了6个手术切除的非肿瘤组织标本（4个正常胰腺组织标本和2个慢性胰腺炎组织标本）、8个胰腺囊性肿瘤（5个导管内乳头状黏液腺瘤、1个浆液性囊腺瘤和2个实性假乳头状肿瘤）以及15个胰腺导管细胞癌中的HMGI(Y)表达。免疫组织化学分析显示，胰腺癌细胞中有强烈的核染色，而非肿瘤细胞中仅可见非常微弱的核染色。HMGI(Y)蛋白过表达与癌症诊断之间存在很强的相关性（P = 0.000018）。因此，HMGI(Y)蛋白表达水平的升高显然与胰腺组织中的恶性表型相关。此外，在两个表现出细胞异型性的囊性肿瘤中也明显存在低水平的蛋白表达，但在未表现出细胞异型性的肿瘤中则没有。基于这些发现，我们提出HMGI(Y)蛋白可能与胰腺肿瘤发生密切相关，并且HMGI(Y)可作为一种潜在的诊断分子标志物，用于明确区分胰腺恶性肿瘤与正常组织或良性病变。
