ANTIBODIES AND ANTIGENS IN HEPATOCELLULAR CARCINOMA

肝细胞癌中的抗体和抗原

• 批准号: 6686330
• 负责人: Eng M TAN
• 金额: $ 35.21万
• 依托单位: SCRIPPS RESEARCH INSTITUTE, THE
• 依托单位国家: 美国
• 财政年份: 1992
• 资助国家: 美国
• 起止时间: 1992-04-01 至 2005-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6686330
• 关键词: antinuclear autoantibody; autoantigens; carcinogenesis; clinical research; complementary DNA; fibroblasts; genetically modified animals; hepatocellular carcinoma; human subject; insulinlike growth factor; laboratory mouse; molecular oncology; neoplasm /cancer immunology; nuclear proteins; protein structure function; tumor antigens

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.

描述（申请人的摘要）：该研究项目利用 肝细胞癌 (HCC) 和其他类型患者的自身抗体 癌症的分离目标抗原。其原理是细胞内 参与致癌作用的蛋白质会引发自身抗体 反应，因此自身抗体可用于免疫筛选 cDNA 表达文库，用于分离、鉴定和表征可能的蛋白质 参与恶变。该应用程序主要关注两个 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) 前导 3 mRNA，受发育调节， 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 HCC组织标本，推测自身抗体代表免疫 系统识别出这种异常表达。谭博士建议生产 转基因小鼠预期 p62 异位表达将导致 IGF-II 表达上调和肿瘤形成，因为 许多研究表明 IGF-II 与致癌有关。我们还将 研究 p62 的其他潜在靶标，可能的候选靶标是蛋白质 p90 似乎是一种经常与 p62 异位相关的自身抗原 表达。第二个项目是分析癌症中另一种新型自身抗原 称为 SG2NA，是一种在 S 期和 G2 期高表达的核蛋白。 细胞周期。 SG2NA N 末端的一个结构域具有转录功能 激活财产并建议进行研究以确定这是否 激活结构域参与鸡胚成纤维细胞的转化 化验。其他研究是确定 SG2NA 的靶基因和 潜在的蛋白质结合伙伴。性质和功能的阐明 这些蛋白质的研究可能有助于理解共激活因子 致癌作用。