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.
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.
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发表时间：
1996-11
期刊：
影响因子：
11.2
通讯作者：
D. Wolf;Shuo Wang;Marilyn Panzica;N. Bassily;N. Thompson;N. Thompson
中科院分区：
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作者：
D. Wolf;Shuo Wang;Marilyn Panzica;N. Bassily;N. Thompson;N. Thompson
大鼠肝癌胎基因TA1和人淋巴细胞激活基因E16编码的多肽与最近在曼氏血吸虫和秀丽线虫中发现的编码区具有高度的同源性。以前的研究表明，TA1/E16的表达上调与大鼠肝癌的发生和人类肿瘤细胞系有关；因此，我们分析了几种原发的人类肿瘤，包括20例结肠癌，以评估TA1/E16的RNA和蛋白表达与肿瘤发生的关系。除1例结直肠癌外，其余均检测到4.0kb转录本，而在正常结肠或炎症性肠病标本中未检测到该转录本。稳定状态的TA1/E16mRNA水平在不同的癌症之间差异很大，并且不是简单地与有丝分裂指数、改良的Dukes‘s分期或肿瘤大小相关。在乳腺癌、子宫内膜、唾液腺和食道腺癌中也检测到TA1/E16基因。用抗TA1/E16多肽的抗体进行Western印迹分析，在肿瘤组织中发现了大约35 kDa和19 kDa的主要反应带，但在正常组织中没有。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，而正常上皮细胞呈阴性。TA1/E16在绒毛状腺瘤伴局限性粘膜内腺癌中呈异质性表达，而在管状腺瘤中呈阴性表达，提示TA1/E16的表达可能与结肠癌的进展有关。该基因在多种人类癌症中的上调表明，该基因在致癌过程中具有共同作用，并可能作为肿瘤标记物应用。
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.