Inhibition of proliferation by 1-8U in interferon-alpha-responsive and non-responsive cell lines.
Interferon (IFN)-inducible proteins of the 1-8 gene family mediate homotypic adhesion and transduction of antiproliferative signals. Their induction correlates with inhibition of cell growth while they are often repressed in the course of malignant transformation and tumor development. Ras-mediated transformation of mouse mast cells is associated with downregulation of 1-8U expression and interferon-alpha (IFN-alpha) treatment reverts the proliferation rate to normal levels together with induction of 1-8U. Conversely, the antiproliferative responses of IFN-alpha in sensitive human melanoma cells are accompanied by 1-8U induction. Here we provide direct evidence that recombinant expression of 1-8U in human cell lines is sufficient to block cell proliferation. Based on the abundant expression and subcellular localization to the plasma membrane and exosome-like structures, we propose a model capable of explaining the pleiotropic functions of 1-8 family proteins in tumor cells and during normal development.
Brem
R
R
Roche Center for Medical Genomics, F. Hoffmann-La Roche, Ltd., Postfach, 4070 Basel, Switzerland.
Oraszlan-Szovik
K
K
Foser
S
S
Bohrmann
B
B
Certa
U
U
D000818:Animals; D001483:Base Sequence; D002455:Cell Division / Q000187:drug effects* / Q000235:genetics / Q000502:physiology*; D002460:Cell Line; D004274:DNA, Recombinant / Q000235:genetics; D020869:Gene Expression Profiling; D011905:Genes, ras; D006801:Humans; D007370:Interferon Type I / Q000494:pharmacology*; D008407:Mast Cells / Q000166:cytology / Q000187:drug effects; D008545:Melanoma / Q000188:drug therapy / Q000235:genetics / Q000473:pathology; D008565:Membrane Proteins / Q000235:genetics / Q000502:physiology*; D051379:Mice; D008954:Models, Biological; D020411:Oligonucleotide Array Sequence Analysis; D016601:RNA-Binding Proteins / Q000235:genetics / Q000502:physiology*; D011994:Recombinant Proteins / Q000235:genetics; D014162:Transfection; D014407:Tumor Cells, Cultured
D004274:DNA, Recombinant; C080082:IFITM3 protein, human; D007370:Interferon Type I; D008565:Membrane Proteins; D016601:RNA-Binding Proteins; D011994:Recombinant Proteins