title: Different molecular mechanisms lead to same endpoints with different function: TNF-alpha induces non-functional CSF-1 receptors on HL-60 cells in contrast to interferon-gamma.
abstract: Tumour necrosis factor-alpha (TNF-alpha) induces differentiation on human promyelocytic leukemia cells (HL-60) as assessed by growth inhibition accompanied by reduction of c-myc levels, and expression of surface colony-stimulating factor-1 (CSF-1) receptors reported as molecular markers for acute myeloid leukemia (AML). CSF-1 receptors can be readily demonstrated by direct binding of 125I-CSF-1 and expression of v-fms whose gene product retains a complete ligand binding domain. Although the same findings have been previously demonstrated on HL-60 cells after interferon-gamma (IFN-gamma) treatment, the major difference between the two pathways of cellular differentiation is the functional state of the induced receptors: when IFN-gamma is used as differentiation agent, the cells are driven to express a high number of CSF-1 receptors and are able to respond to a CSF-1 stimulus. Such mitogenic response is not obtained when TNF-alpha is applied as inducer indicating that the newly expressed receptors are not functional. This difference may be due to different molecular mechanisms the two factors trigger in order to reach the same endpoint: the maturation of this leukemic population.
authors.affiliation: Institute of Molecular Biology and Biotechnology (IMBB), Heraklion, Crete, Greece.
authors.forename: S
authors.initials: S
authors.lastname: Vassiliadis
authors.forename: L
authors.initials: L
authors.lastname: Guilbert
authors.forename: N
authors.initials: N
authors.lastname: Kyrpides
authors.forename: J
authors.initials: J
authors.lastname: Papamatheakis
mesh_terms: D002454:Cell Differentiation / Q000187:drug effects; D006801:Humans; D007371:Interferon-gamma / Q000494:pharmacology*; D015473:Leukemia, Promyelocytic, Acute / Q000473:pathology; D016186:Receptor, Macrophage Colony-Stimulating Factor / Q000032:analysis*; D014407:Tumor Cells, Cultured; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology*
chemical_list: D014409:Tumor Necrosis Factor-alpha; D007371:Interferon-gamma; D016186:Receptor, Macrophage Colony-Stimulating Factor