The Fanconi anemia group C gene product modulates apoptotic responses to tumor necrosis factor-α and Fas ligand but does not suppress expression of receptors of the tumor necrosis factor receptor superfamily

Paul S. Koh, Grant C. Hughes, Gregory R. Faulkner, Winifred W. Keeble, Grover C. Bagby

    Research output: Contribution to journalArticle

    29 Citations (Scopus)

    Abstract

    Exposure of hematopoietic progenitor cells (HPC) from mice and humans with Fanconi anemia group C (FAC) to interferon-γ (IFN-γ) or tumor necrosis factor-α (TNF-α) at doses too low to inhibit growth of normal HPC induces profound apoptotic responses. Because the IFN-γ hypersensitivity of cells lacking the FAC protein is mediated, in part, through priming of the Fas pathway, and because several other members of this family are capable of inducing apoptosis either alone or in concert with each other, we tested the hypothesis that IFN-γ induces increased expression of members of the TNF receptor (TNFR) superfamily in cells nullizygous for the FAC gene. Using isogenic human Epstein-Barr virus-transformed lymphoblast cell lines and c- kit+ bone marrow cells from mice with inactivating mutations of the FAC locus, we quantified mRNA levels by reverse transcriptase polymerase chain reaction and surface expression of the gene products by flow cytometry of TNFR1, TNFR2, Fas, CD30, CD40, and nerve growth factor receptor. We found that neither constitutive nor IFN-γ-induced expression of these receptors was influenced by the absence of a functional FAC gene product, and expression of these receptors was not suppressed in nullizygous cells complemented with the normal FAC cDNA. We conclude that, although exaggerated apoptotic responses in FAC-deficient cells are at least partially mediated through activation of members of the TNFR superfamily, the normal FAC protein does not function as a direct suppressor of this family of molecules and inactivation of FAC does not augment expression of these proteins.

    Original languageEnglish (US)
    Pages (from-to)1-8
    Number of pages8
    JournalExperimental Hematology
    Volume27
    Issue number1
    DOIs
    StatePublished - Jan 1999

    Fingerprint

    Fanconi Anemia
    Fas Ligand Protein
    Tumor Necrosis Factor Receptors
    Tumor Necrosis Factor-alpha
    Fanconi Anemia Complementation Group C Protein
    Interferons
    Genes
    Hematopoietic Stem Cells
    Receptors, Tumor Necrosis Factor, Type II
    Receptors, Tumor Necrosis Factor, Type I
    Nerve Growth Factor Receptor
    Transformed Cell Line
    Gene Flow
    Reverse Transcriptase Polymerase Chain Reaction
    Human Herpesvirus 4
    Bone Marrow Cells
    Flow Cytometry
    Hypersensitivity
    Complementary DNA
    Apoptosis

    Keywords

    • Apoptosis
    • Fanconi anemia
    • Interferon-gamma
    • Tumor necrosis factor receptor superfamily

    ASJC Scopus subject areas

    • Cancer Research
    • Cell Biology
    • Genetics
    • Hematology
    • Oncology
    • Transplantation

    Cite this

    The Fanconi anemia group C gene product modulates apoptotic responses to tumor necrosis factor-α and Fas ligand but does not suppress expression of receptors of the tumor necrosis factor receptor superfamily. / Koh, Paul S.; Hughes, Grant C.; Faulkner, Gregory R.; Keeble, Winifred W.; Bagby, Grover C.

    In: Experimental Hematology, Vol. 27, No. 1, 01.1999, p. 1-8.

    Research output: Contribution to journalArticle

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