Hydroquinone modulates the GM-CSF signaling pathway in TF-1 cells

• Published in: Leukemia Vol. 18; no. 7; pp. 1296 - 1304
• Main Authors: ZHENG, J. H, PYATT, D. W, GROSS, S. A, LE, A. T, KERZIC, P. J, IRONS, R. D
• Format: Journal Article
• Language: English
• Published: London Nature Publishing 01.07.2004; Nature Publishing Group
• Subjects: Acute myeloid leukemia; Alkylation; Antigens, CD34; Benzene; Biological and medical sciences; Bone marrow; Bone Marrow Cells - cytology; Bone Marrow Cells - drug effects; Carcinogens - pharmacology; CD34 antigen; Cell division; Cell Division - drug effects; Cell Line, Tumor; Cell proliferation; Chemotherapy; Colonies; Colony-stimulating factor; Cytokines; Deoxyribonucleic acid; DNA; Erythroleukemia; Extracellular signal-regulated kinase; Granulocyte-macrophage colony-stimulating factor; Granulocyte-Macrophage Colony-Stimulating Factor - biosynthesis; Granulocyte-Macrophage Colony-Stimulating Factor - metabolism; Granulocyte-Macrophage Colony-Stimulating Factor - pharmacology; Granulocytes; Health sciences; Hematologic and hematopoietic diseases; Humans; Hydrocarbons; Hydroquinone; Hydroquinones - pharmacology; Kinases; Kinetics; Leukemia; Leukemia, Erythroblastic, Acute - pathology; Leukemia, Myeloid, Acute - chemically induced; Medical sciences; Metabolic pathways; Metabolites; Mitogen-Activated Protein Kinases - metabolism; Pathogenesis; Phosphorylation; Recombinant Proteins; Reporter gene; Signal transduction; Signal Transduction - drug effects; Signaling; Transcription activation; Transcription Factor AP-1 - metabolism; Transcription factors; United States > US; Cell proliferation; Extracellular signal-regulated protein kinase; Hematology; Enzyme; Mitogen-activated protein kinase; activator protein-1 (AP-1); Antioxidant; GM-CSF signaling; Hydroquinone; Signal transduction; Signaling pathway; activation of ERK; hydroquinone (HQ); Colony stimulating factor 1; Granulocyte macrophage colony stimulating factor; Transcription factor AP1
• ISSN: 0887-6924; 1476-5551
• DOI: 10.1038/sj.leu.2403389

Human leukemogens, including alkylating chemotherapeutic agents and benzene, enhance granulocyte-macrophage colony-stimulating factor (GM-CSF)-dependent proliferation of human CD34+ bone marrow (BM) cells. The extracellular signal-regulated kinase (ERK) pathway plays an important role in GM-CSF-dependent proliferation and also has been implicated in the pathogenesis of acute myelogenous leukemia. Therefore, we investigated the effects of the benzene metabolite, hydroquinone (HQ), on alterations in the GM-CSF signaling pathway in TF-1 erythroleukemia cells and human CD34+ BM cells. HQ treatment in TF-1 cells results in a strong proliferative response that is dependent on ERK activation and GM-CSF production. HQ also induces ERK-dependent AP-1 activation with concomitant increased transcriptional activity of AP-1 reporter gene. However, the kinetics of ERK activation are different between rhGM-CSF and HQ in TF-1 cells: rhGM-CSF results in immediate activation of ERK, whereas HQ activation of ERK is delayed. Further, HQ and rhGM-CSF together produce an immediate increase in ERK phosphorylation, which is sustained for over 48 h. HQ also stimulates colony formation, AP-1 DNA binding and GM-CSF production in human CD34+ BM cells. These results suggest that HQ stimulates proliferation via activation of ERK/AP-1 and is at least partially mediated via the production of GM-CSF.