TRANSFORMING GENES IN EXPERIMENTAL ONCOGENESIS AND HUMAN CANCER

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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.