CELLULAR ACTIONS OF TRANSFORMING GROWTH FACTORS

  • Magun, Bruce (PI)

    Project: Research project

    Project Details

    Description

    Since the discovery that specific polypeptide factors termed transforming
    growth factors (TGFs) were able to confer the transformed phenotype to
    otherwise normal cells, elucidation of their mechanisms of action has been
    a goal in cancer research. Over the past few years a great deal of effort
    has been expended in the isolation and purification of TGFs, since
    mechanistic studies require the use of purified molecules. Recently,
    highly purified preparations of TGFs (TGF-alpha and TGF-beta) have been
    obtained, thereby paving the way for attempts to determine their mechanisms
    of action and the set of specific cellular responses which they elicit.
    This research intends to address questions regarding the identity of
    specific cell-surface TGF receptors, their involvement in mediating
    TGF-associated responses, and the specific intracellular consequences of
    TGF action. Efforts will continue to purify TGF-alpha and TGF-beta from
    rat fetuses, utilizing chromatography, isoelectric focusing, and HPLC
    methods. Purified TGFs will be iodinated in order to elucidate their
    characteristics of binding to cell surfaces of nontransformed and
    transformed mouse and rat cells. The characteristics of endocytosis and
    intracellular processing of 125 I-TGFs will be investigated, with emphasis
    on intracellular sites of TGF processing. Photoaffinity labeling of TGF
    receptors will be employed to demonstrate their molecular weight
    characteristics and to determine the intracellular localization of
    GF-receptor complexes. Clones of cDNAs homologous to genes induced by
    TGF-alpha and TGF-beta in mouse and rat cells will be obtained in plasmid
    and phage vectors. These cDNA clones will be employed to determine whether
    TGF-alpha and TGF-beta induce the same or different gene products and if
    EGF-\and TGF-alpha induce similar gene products. The ability of the tumor
    promoter TPA to induce gene products similar to those induced by TGFs will
    also be determined. The endogenous level of expression of TGF-induced
    genes in transformed cells will be compared to the level found in normal
    cells. Finally, the ability of lysosomotropic agents to inhibit
    TGF-induced expression of specific gene products will be investigated. (J)
    StatusFinished
    Effective start/end date7/1/846/30/87

    Funding

    • National Institutes of Health
    • National Institutes of Health
    • National Institutes of Health

    ASJC

    • Medicine(all)

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