ANTIBODIES AND ANTIGENS IN HEPATOCELLULAR CARCINOMA

描述(申请者摘要)：本研究项目利用 肝细胞癌及其他类型患者的自身抗体 以分离靶抗原。其基本原理是细胞内 与致癌有关的蛋白质正在引发自身抗体。 因此自身抗体可用于免疫筛选cDNAs 表达文库用于分离、鉴定和鉴定可能 参与恶变。这个应用程序侧重于两个 新抗原：P62和SG2Na。P62与胰岛素样生长因子-II结合 信使RNA(IGF-II mRNA)Leader3mRNA是发育调节的， 在胎儿组织中表达，但在成人组织中不表达。初步研究表明 P62在至少25%的癌症结节中异位表达。 肝细胞癌组织标本，推测自身抗体代表免疫 对这种异常表达的系统识别。谭博士建议制作一种 转基因小鼠，预期p62的异位表达将导致 胰岛素样生长因子-II表达上调与肿瘤形成 在许多研究中，IGF-II与癌症的发生有关。我们还将 研究p62的其他潜在靶点，一个可能的候选者是蛋白质 P90似乎是一种经常与p62异位相关联的自身抗原 表情。第二个项目是分析癌症中的另一种新的自身抗原。 SG2NA是一种核蛋白，在S和G2期高度表达 细胞周期。SG2NA N-末端的一个结构域具有转录功能 提出了激活性质和研究来确定这是否 激活结构域参与鸡胚胎成纤维细胞转化 化验。另一项研究是确定SG2NA的靶基因(S)和 潜在的蛋白质结合伙伴。阐明其性质和功能 这些蛋白的相互作用可能有助于理解 致癌。

DESCRIPTION (Applicants' Abstract): This research project makes use of autoantibodies in patients with hepatocellular carcinoma (HCC) and other types of cancer to isolate target antigens. The rationale is that intracellular proteins, which are involved in carcinogenesis, are provoking autoantibody responses and therefore autoantibodies can be used to immunoscreen cDNA expression libraries to isolate, identify and characterize proteins which might be involved in malignant transformation. This application is focused on two novel antigens: p62 and SG2Na. P62 binds to Insulin-like growth factor-II messenger RNA (IGF-II mRNA) leader 3 mRNA which is developmentally regulated, expressed in fetal tissues but not in adult tissues. Preliminary studies show that p62 is ectopically expressed in cancer nodules in at least 25 percent of HCC tissue specimens and it is postulated that autoantibodies represent immune system recognition of this aberrant expression. Dr. Tan proposes to produce transgenic mice with the anticipation that p62 ectopic expression will lead to upregulation of IGF-II expression and tumor formation, since high expression of IGF-II has been linked with carcinogenesis in many studies. We will also investigate other potential targets of p62 and a likely candidate is a protein p90 that appears to be an autoantigen frequently linked with p62 ectopic expression. A second project is analysis of another novel autoantigen in cancer called SG2NA, a nuclear protein that is highly expressed in S and G2 phases of the cell cycle. A domain in the N-terminus of SG2NA has transcription activating property and studies are proposed to determine whether this activation domain is involved in transformation using chicken embryo fibroblast assay. Other studies are to determine the target genes(s) of SG2NA and potential protein binding partners. Elucidation of the properties and function of these proteins might contribute to understanding co-activating factors in carcinogenesis.