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一种高度保守的癌胚基因TA1/E16在人结肠癌及其他原发性癌症中的表达:与曼氏血吸虫氨基酸通透酶及秀丽隐杆线虫基因产物的同源性

Expression of a highly conserved oncofetal gene, TA1/E16, in human colon carcinoma and other primary cancers: homology to Schistosoma mansoni amino acid permease and Caenorhabditis elegans gene products.

作者信息

Wolf D A, Wang S, Panzica M A, Bassily N H, Thompson N L

机构信息

Department of Pathology, Rhode Island Hospital and Brown University School of Medicine, Providence, Rhode Island 02903, USA.

出版信息

Cancer Res. 1996 Nov 1;56(21):5012-22.

PMID:8895758
Abstract

The peptides encoded by the rat liver oncofetal cDNA TA1 and the human lymphocyte activation gene E16 display a high degree of homology with coding regions recently identified in Schistosoma mansoni and Caenorhabditis elegans. Previous studies showed that up-regulation of TA1/ E16 expression was associated with rat hepatocarcinogenesis and human tumor cell lines; therefore, we analyzed several primary human tumors including a panel of 20 colon carcinomas to evaluate the relationship of TA1/E16 RNA and protein expression to neoplasia. A 4.0-kb transcript was detected in all but one colorectal carcinoma but not in normal colon or specimens of inflammatory bowel disease. Steady-state TA1/E16 mRNA levels varied considerably between carcinomas and did not correlate simply with mitotic index, modified Dukes' stage, or tumor size. TA1/E16 message also was detected in adenocarcinomas from breast, endometrium, salivary gland, and esophagus. Western blot analysis using antibodies against TA1/E16-deduced peptides identified major reactive bands of approximately 35 and 19 kDa in neoplasms but not in normal tissue. Immunoperoxidase staining localized the protein primarily to the supranuclear region of colon carcinoma cells, whereas normal epithelial cells were negative. Heterogeneous staining was found in villous adenomas with focal intramucosal adenocarcinoma but was negative in tubular adenomas, suggesting that expression of TA1/E16 may correlate with neoplastic progression in the colon. Up-regulation of this gene in various human cancers suggests a common role in the carcinogenic process and possible application as a tumor marker.

摘要

大鼠肝脏癌胚cDNA TA1和人类淋巴细胞激活基因E16编码的肽与最近在曼氏血吸虫和秀丽隐杆线虫中鉴定出的编码区域显示出高度同源性。先前的研究表明,TA1/E16表达的上调与大鼠肝癌发生和人类肿瘤细胞系有关;因此,我们分析了几种原发性人类肿瘤,包括一组20例结肠癌,以评估TA1/E16 RNA和蛋白质表达与肿瘤形成的关系。在除一例之外的所有结直肠癌中均检测到一个4.0-kb的转录本,但在正常结肠或炎症性肠病标本中未检测到。癌组织之间的TA1/E16 mRNA稳态水平差异很大,且与有丝分裂指数、改良的杜克分期或肿瘤大小并无简单的相关性。在乳腺癌、子宫内膜癌、唾液腺癌和食管癌的腺癌中也检测到了TA1/E16信息。使用针对TA1/E16推导肽的抗体进行的蛋白质印迹分析在肿瘤组织中鉴定出约35 kDa和19 kDa的主要反应条带,而在正常组织中未检测到。免疫过氧化物酶染色显示该蛋白主要定位于结肠癌细胞的核上区域,而正常上皮细胞呈阴性。在伴有局灶性黏膜内腺癌的绒毛状腺瘤中发现异质性染色,但在管状腺瘤中呈阴性,这表明TA1/E16的表达可能与结肠肿瘤的进展相关。该基因在各种人类癌症中的上调表明其在致癌过程中具有共同作用,并有可能作为肿瘤标志物应用。

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