title: GM-CSF rescues TF-1 cells from growth factor withdrawal-induced, but not differentiation-induced apoptosis: the role of BCL-2 and MCL-1.
abstract: Cytokines such as granulocyte-macrophage colony-stimulating factor (GM-CSF) and IL-3 promote the survival and stimulate the proliferation of haematopoietic cells. Using the GM-CSF-dependent TF-1 myeloid leukaemia cell line, the authors show that the endogenous levels of BCL-2 and MCL-1 are downregulated upon GM-CSF withdrawal, whereas the levels of BCL-x(L)and Bax are unchanged. Re-exposure of growth factor deprived cells to GM-CSF resulted in an early and transient increase in MCL-1 expression, and prolonged induction of BCL-2, which prevented apoptosis. In contrast, the expression of BCL-2 and MCL-1 were not modulated during TPA-induced differentiation of TF-1 cells, which was followed by apoptosis despite the presence of GM-CSF. TF-1 cells overexpressing BCL-2 or MCL-1 underwent delayed apoptosis upon growth factor withdrawal, but displayed no impaired apoptosis in response to TPA. Erythropoietin (Epo) induced the expression of BCL-2 and MCL-1 protein in TF-1 cells, however it did not support their long term proliferation, further demonstrating that upregulation of these anti-apoptotic genes is insufficient for the long term proliferation of TF-1 cells.
authors.affiliation: Laboratory of Molecular Aspects of Hematopoiesis, Memorial Sloan-Kettering Cancer Center, 1275 York Avenue, New York, NY, 10021, USA.
authors.forename: L
authors.initials: L
authors.lastname: Klampfer
authors.forename: J
authors.initials: J
authors.lastname: Zhang
authors.forename: S D
authors.initials: SD
authors.lastname: Nimer
mesh_terms: D017209:Apoptosis / Q000187:drug effects*; D002454:Cell Differentiation / Q000187:drug effects / Q000502:physiology; D002470:Cell Survival / Q000187:drug effects / Q000235:genetics; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000494:pharmacology*; D006133:Growth Substances / Q000172:deficiency / Q000494:pharmacology*; D006801:Humans; D007951:Leukemia, Myeloid / Q000378:metabolism* / Q000473:pathology; D064549:Myeloid Cell Leukemia Sequence 1 Protein; D009363:Neoplasm Proteins / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D013997:Time Factors; D014162:Transfection; D014407:Tumor Cells, Cultured
chemical_list: D006133:Growth Substances; D064549:Myeloid Cell Leukemia Sequence 1 Protein; D009363:Neoplasm Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D013755:Tetradecanoylphorbol Acetate