TRANSFORMING GENES IN EXPERIMENTAL ONCOGENESIS AND HUMAN CANCER

过去一年的一些亮点包括：(1)演示 活化的血小板衍生生长因子(PDGF)自分泌途径和 它在人肿瘤细胞体外增殖中的作用；(2)论证 PDGF受体激活在细胞转化和人类恶性肿瘤中的作用； (3)发现PDGF B的5个氨基酸取代将PDGF A转化为 PDGF B样转化分子；(4)PDGF对GTP酶的刺激 激活对照蛋白酪氨酸磷酸化和c-H-ras- NIH/3T3细胞表达与p21ras激活相关； 阐明α和β底物特异性的差异 PDGF受体；(6)PDGF受体的扩增和过表达 和表皮生长因子受体在人脑胶质瘤中的表达； ErbB-3酪氨酸激酶介导的配体依赖性信号转导 及其在人乳腺肿瘤细胞中的结构性激活； 具有生物活性的重组角质形成细胞生长因子的表达 (9)KGF多基因家族在类人猿中的出现 (10)KGF和肝细胞生长因子(HGF)是肝素- 成纤维细胞中肺泡II型细胞结合生长因子的研究 条件培养液；(11)证明MET原癌基因是 酪氨酸激酶生长因子受体与肝细胞生长 因子/分散因子(HGF/SF)及其致瘤潜能和信号转导 途径；(12)KGF受体衍生多肽拮抗剂识别部分 (13)用一种策略克隆表达的c DNA 为分离新的基因和它们的蛋白质而在这个实验室开发的 产品包括双特异性磷酸酶(VHR)、EST和 野生型Galpha12基因产物；(14)证明H-ras和RAF-1 合作转化NIH/3T3成纤维细胞；和(15)普通 因子依赖中IL-4和胰岛素信号转导途径中的元件 造血细胞。

Some of the highlights of the past year include: (1) demonstration of an activated platelet-derived growth factor (PDGF) autocrine pathway and its role in human tumor cell proliferation in vitro; (2) demonstration of PDGF receptor activation in cell transformation and human malignancy; (3) finding that five PDGF B amino acid substitutions convert PDGF A to a PDGF B-like transforming molecule; (4) PDGF stimulation of GTPase- activating protein tyrosine phosphorylation in control and c-H-ras- expressing NIH/3T3 cells correlates with p21ras activation; (5) elucidation of differences in substrate specificities of alpha and beta PDGF receptors; (6) amplification and overexpression of PDGF receptors and epidermal growth factor (EGF) receptor in human glial tumors; (7) demonstration of ligand-dependent signaling by the erbB-3 tyrosine kinase and its constitutive activation in human breast tumor cells; (8) expression of biologically active recombinant keratinocyte growth factor (KGF); (9) emergence of the KGF multigene family during the great ape radiation; (10) KGF and hepatocyte growth factor (HGF) are heparin- binding growth factors for alveolar type II cells in fibroblast conditioned medium; (11) demonstration that the met proto-oncogene is the tyrosine kinase growth factor receptor for the hepatocyte growth factor/scatter factor (HGF/SF), its tumorigenic potential and signaling pathway; (12) a KGF receptor-derived peptide antagonist identifies part of the ligand-binding site; (13) expression cDNA cloning by a strategy developed in this laboratory to isolate novel genes and their protein products including a dual-specificity phosphatase (VHR), est, and the wild-type Galpha12 gene product; (14) demonstration that H-ras and raf-1 cooperate in transformation of NIH/3T3 fibroblasts; and (15) common elements in IL-4 and insulin signaling pathways in factor-dependent hematopoietic cells.