TRANSFORMING GENES IN EXPERIMENTAL ONCOGENESIS AND HUMAN CANCER

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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.