TRANSFORMING GENES IN EXPERIMENTAL ONCOGENESIS AND HUMAN CANCER

实验性癌发生和人类癌症中的基因转化

• 批准号: 3838322
• 负责人: S A AARONSON
• 金额: --
• 依托单位: DIVISION OF CANCER EPIDEMIOLOGY AND GENETICS
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/3838322
• 关键词: RNA splicing; autocrine; biological signal transduction; bladder neoplasm; cell differentiation; cell growth regulation; cellular oncology; chemotaxis; chimeric proteins; colony stimulating factor; complementary DNA; epidermal growth factor; fibroblast growth factor; fibroblasts; gene deletion mutation; gene expression; growth factor; growth factor receptors; guanine nucleotides; human genetic material tag; human tissue; keratinocyte; liver cells; mammary epithelium; mitogens; molecular cloning; neoplasm /cancer genetics; neoplastic transformation; nucleic acid hybridization; nucleic acid sequence; oncogenes; oncoproteins; phosphatidylinositols; platelet derived growth factor; protein structure function; protein tyrosine kinase; protooncogene; receptor binding; receptor coupling; retinoblastoma; tissue /cell culture; transfection; tumor suppressor genes

Some of the highlights of the past year include: (1) Growth factor signalling pathways and their alterations in human tumors; (2) identification of a competitive hepatocyte growth factor (HGF) antagonist encoded by an alternative transcript; (3) cloning, expression and biological effects of the erbB-2/neu gene in mammalian cells; (4) catalysis of guanine nucleotide exchange on the CDC42Hs protein by the dbl oncogene product; (5) role of alfa beta receptor heterodimer formation in beta platelet-derived growth factor (PDGF) receptor activation by PDGF-AB; (6) a deletion in the extracellular domain of the a PDGF receptor differentially impairs PDGF-AA and PDGF-BB binding affinities; (7) demonstration of an activated PDGF autocrine pathway and its role in human tumor cell proliferation in vitro; (8) detection and isolation of novel protein-tyrosine kinase genes employing reduced stringency hybridization; (9) variant PDGF ligands and receptor- structure-function relationships; (10) a novel mechanism regulating growth factor association with the cell surface: identification of a PDGF retention domain; (11) determination of ligand-binding specificity by alternative splicing: two distinct growth factor receptors encoded by a single gene; (12) keratinocyte growth factor (KGF) receptor: transforming potential on fibroblasts and epithelial cell-specific expression by alternative splicing; (13) development of a highly efficient expression cDNA cloning system: application to oncogene isolation; (14) oncogenic potential of erbB-2 in human mammary epithelial cells; (15) a region of proto-dbl essential for its transforming activity shows sequence similarity to a yeast cell cycle gene, CDC24, and the human breakpoint cluster gene, bcr; (16) mouse PDGF receptor a gene is deleted in W19H and patch mutations on chromosome 5; (17) the retinoblastoma gene functions as a growth and tumor suppressor in human bladder carcinoma cells; and (18) tyrosine mutations within the a PDGF receptor kinase insert domain abrogate receptor-associated phosphatidylinositol-3 kinase activity without affecting mitogenic or chemotactic signal transduction.

过去一年的一些亮点包括：（1）增长因素 信号通路及其在人类肿瘤中的改变;（2） 肝细胞生长因子（HGF）竞争性拮抗剂鉴定 （3）克隆、表达和鉴定; erbB-2/neu基因在哺乳动物细胞中的生物学效应;（4） 在CDC 42 Hs蛋白上的鸟嘌呤核苷酸交换的催化作用 dbl癌基因产物;（5）α β受体异源二聚体的作用 β血小板衍生生长因子（PDGF）受体形成 （6）PDGF-AB的细胞外结构域中的缺失; a PDGF受体差异性地损害PDGF-AA和PDGF-BB结合 （7）激活的PDGF自分泌途径的证明， 其在体外人肿瘤细胞增殖中的作用;（8）检测和 使用还原的方法分离新的蛋白酪氨酸激酶基因 （9）变体PDGF配体和受体- 结构-功能关系;（10）一种新的调节机制 与细胞表面结合的生长因子：PDGF的鉴定 保留结构域;（11）通过测定配体结合特异性 选择性剪接：两种不同的生长因子受体编码的一个 单基因;（12）角质细胞生长因子（KGF）受体：转化 对成纤维细胞和上皮细胞特异性表达的潜力， 选择性剪接;（13）开发高效表达 cDNA克隆系统：应用于癌基因分离;（14）致癌 erbB-2在人乳腺上皮细胞中的潜力;（15） 转化活性所必需的原DBL序列 与酵母细胞周期基因CDC 24和人类断裂点相似 簇基因，bcr;（16）小鼠PDGF受体a基因在W19 H中缺失， 5号染色体上的补丁突变;（17）视网膜母细胞瘤基因功能 作为人膀胱癌细胞的生长和肿瘤抑制剂;和 (18)PDGF受体激酶插入结构域内的酪氨酸突变 消除受体相关磷脂酰肌醇-3激酶活性 而不影响促有丝分裂或趋化性信号转导。