Hydroquinone modulates the GM-CSF signaling pathway in TF-1 cells
| Autor: | Anh T. Le, Richard D. Irons, Patrick J. Kerzic, Jia Hua Zheng, Sherilyn A. Gross, David W. Pyatt |
|---|---|
| Rok vydání: | 2004 |
| Předmět: |
Macrophage colony-stimulating factor
MAPK/ERK pathway Cancer Research Antigens CD34 Bone Marrow Cells Cell Line Tumor medicine Humans Phosphorylation biology Cell growth Kinase Granulocyte-Macrophage Colony-Stimulating Factor Hematology Recombinant Proteins Hydroquinones Cell biology Transcription Factor AP-1 Kinetics Leukemia Myeloid Acute Granulocyte macrophage colony-stimulating factor Oncology Cell culture Mitogen-activated protein kinase Carcinogens biology.protein Cancer research Leukemia Erythroblastic Acute Mitogen-Activated Protein Kinases Signal transduction Cell Division Signal Transduction medicine.drug |
| Zdroj: | Leukemia. 18:1296-1304 |
| ISSN: | 1476-5551 0887-6924 |
| DOI: | 10.1038/sj.leu.2403389 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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