TRANSFORMING GENES IN EXPERIMENTAL ONCOGENESIS AND HUMAN CANCER

过去一年的一些亮点包括：(1)增长因素 人类肿瘤中的信号通路及其变化； 一种竞争性肝细胞生长因子拮抗剂的鉴定 由替代转录本编码；(3)克隆、表达和 ErbB-2/neu基因在哺乳动物细胞中的生物学效应 鸟嘌呤核苷酸交换对CDC42Hs蛋白的催化作用 Dbl癌基因产物；(5)αβ受体异源二聚体的作用 β-血小板衍生生长因子受体的形成 由PDGF-AB激活；(6)细胞外域的缺失 PDGF受体对PDGF-AA和PDGF-BB结合的不同损伤作用 亲和力；(7)激活的PDGF自分泌途径和 它在人肿瘤细胞体外增殖中的作用；(8)检测和 利用Reduced技术分离新的蛋白酪氨酸激酶基因 严格杂交；(9)PDGF变异体配体和受体- 结构-功能关系；(10)一种新的调节机制 与细胞表面相关的生长因子：一种PDGF的鉴定 保留结构域；(11)通过以下方法测定配体结合专一性 选择性剪接：两种不同的生长因子受体，由一种 单基因；(12)角质形成细胞生长因子受体：转化 对成纤维细胞和上皮细胞特异性表达的潜在影响 选择性剪接；(13)开发高效表达 基因克隆系统在癌基因分离中的应用；(14)致癌基因 ErbB-2在人乳腺上皮细胞中的潜能；(15) 其转化活性所必需的原DBL显示序列 与酵母细胞周期基因CDC24和人类断裂点的相似性 簇基因，bcr；(16)小鼠PDGF受体a基因在W19H和 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因子；以及 (18)α-PDGF受体激酶插入结构域内的酪氨酸突变 受体相关磷脂酰肌醇-3激酶活性的研究 而不影响有丝分裂或趋化信号转导。

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.