ANTIBODIES AND ANTIGENS IN HEPATOCELLULAR CARCINOMA

肝细胞癌中的抗体和抗原

• 批准号: 6831649
• 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 2006-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6831649
• 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（申请人摘要）：本研究项目利用 肝细胞癌（HCC）和其他类型患者的自身抗体 来分离靶抗原。基本原理是细胞内 与致癌作用有关的蛋白质会引发自身抗体， 因此自身抗体可用于免疫筛选cDNA 表达文库来分离、鉴定和表征可能 参与恶性转化。该应用程序集中在两个 新抗原：p62和SG 2Na。P62与胰岛素样生长因子-II结合 信使RNA（IGF-II mRNA）前导3 mRNA，其是发育调节的， 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， HCC组织标本，并假定自身抗体代表免疫 系统识别这种异常表达。谭博士建议制作 预期p62异位表达将导致 IGF-II表达和肿瘤形成的上调，因为IGF-II的高表达， 在许多研究中，IGF-II与致癌作用有关。我们还将 研究p62的其他潜在靶点，一个可能的候选者是一种蛋白质， p90似乎是一种经常与p62异位连接的自身抗原， 表情第二个项目是分析另一种新的癌症自身抗原 称为SG 2NA，是一种核蛋白，在S期和G2期高度表达， 细胞周期SG 2NA的N-末端的一个结构域具有转录活性， 建议进行激活特性和研究来确定这是否 激活结构域参与鸡胚成纤维细胞转化 比色法其他研究是确定SG 2NA的靶基因， 潜在的蛋白质结合伴侣。性质和功能说明 这些蛋白质的合成可能有助于了解细胞内的共激活因子。 致癌作用

项目成果

The quantity of nucleolar proteins nucleolin and protein B23 is related to cell doubling time in human cancer cells.

• 发表时间: 1995-10
• 期刊: Laboratory investigation; a journal of technical methods and pathology
• 作者: M. Derenzini;V. Sirri;D. Treré;R. Ochs

Coiled bodies in the nucleolus of breast cancer cells.

乳腺癌细胞核仁中的卷曲体。

• DOI: 10.1242/jcs.107.2.385
• 发表时间: 1994
• 期刊: Journal of cell science
• 影响因子: 4
• 作者: Ochs,RL;SteinJr,TW;Tan,EM
• 通讯作者: Tan,EM

Recursive partitioning as an approach to selection of immune markers for tumor diagnosis.

• 发表时间: 2003-11
• 期刊: Clinical cancer research : an official journal of the American Association for Cancer Research
• 作者: J. Koziol;Jian-ying Zhang;C. Casiano;Xuan Peng;F. Shi;A. Feng;E. Chan;E. Tan

Transcription activating property of autoantigen SG2NA and modulating effect of WD-40 repeats.

自身抗原 SG2NA 的转录激活特性和 WD-40 重复序列的调节作用。

• DOI: 10.1006/excr.2001.5320
• 发表时间: 2001
• 期刊: Experimental cell research.
• 作者: Zhu,W;Chan,EK;Li,J;Hemmerich,P;Tan,EM
• 通讯作者: Tan,EM

Overexpression of the IGF2-mRNA binding protein p62 in transgenic mice induces a steatotic phenotype.

• DOI: 10.1016/j.jhep.2010.08.034
• 发表时间: 2011-05
• 期刊: Journal of hepatology
• 影响因子: 25.7
• 作者: Tybl E;Shi FD;Kessler SM;Tierling S;Walter J;Bohle RM;Wieland S;Zhang J;Tan EM;Kiemer AK
• 通讯作者: Kiemer AK