Sang J, Lim Y P, Panzica M, Finch P, Thompson N L
Department of Medical Oncology, Rhode Island Hospital/Brown University, Providence 02903.
Cancer Res. 1995 Mar 1;55(5):1152-9.
Hepatocellular carcinoma is characterized by changes in gene expression associated with cell growth and differentiation. Cell surface antigenic changes have also been described based on differential antibody reactivity between normal and neoplastic liver. We obtained a novel tumor-associated cDNA designated TA1 on the basis of its differential expression between hepatoma cells and normal liver. Sequence analysis predicted a 723-base pair open reading frame with the deduced amino acid sequence encoding an integral membrane protein containing multiple hydrophobic transmembrane domains. Database searches revealed TA1 as the likely rat homologue of E16, a recently cloned human cDNA associated with lymphocyte activation. Although noncoding sequences diverged significantly, the 95% conservation of the predicted proteins between species strongly suggests an important, although as yet undefined, function in normal cells. TA1 transcripts were detected in normal adult rat tissues including testes, brain, ovary, spleen, mammary gland, and uterus with the highest steady-state expression in placenta. Although no expression was detected in normal liver, all rat hepatomas examined expressed an abundant 3.2-kilobase transcript. TA1 expression was closely associated with progression in this tumor model and suggests this molecule, originally linked to cell activation, also plays a role in the malignant phenotype.
肝细胞癌的特征在于与细胞生长和分化相关的基因表达变化。基于正常肝脏与肿瘤肝脏之间不同的抗体反应性,也描述了细胞表面抗原性变化。我们基于其在肝癌细胞和正常肝脏之间的差异表达,获得了一个名为TA1的新型肿瘤相关cDNA。序列分析预测了一个723个碱基对的开放阅读框,其推导的氨基酸序列编码一个含有多个疏水跨膜结构域的整合膜蛋白。数据库搜索显示TA1可能是E16的大鼠同源物,E16是最近克隆的与淋巴细胞活化相关的人类cDNA。虽然非编码序列有显著差异,但物种间预测蛋白质95%的保守性强烈表明其在正常细胞中具有重要功能,尽管尚未明确。在正常成年大鼠组织中检测到TA1转录本,包括睾丸、脑、卵巢、脾脏、乳腺和子宫,在胎盘中稳态表达最高。虽然在正常肝脏中未检测到表达,但所有检测的大鼠肝癌均表达丰富的3.2千碱基转录本。在该肿瘤模型中,TA1表达与肿瘤进展密切相关,表明该最初与细胞活化相关的分子在恶性表型中也起作用。