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

Leukemia volume 18, pages 1296–1304 (2004)Cite this article

Abstract

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.

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Acknowledgements

We gratefully acknowledge Dr Vasilis Vasiliou for the generous gift of the 4AP-1 reporter gene, Wayne Stillman, Yanzhu Yang, Karen Helm for technical assistance and Ann Louden for the manuscript preparation. We also thank Dr Yanli Ouyang and Dr Ronda Baker for their constructive comments.

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Authors and Affiliations

  1. Molecular Toxicology and Environmental Health Sciences Program, School of Pharmacy, University of Colorado Health Sciences Center, Denver, CO, USA

    J H Zheng, D W Pyatt, S A Gross, A T Le, P J Kerzic & R D Irons

  2. Department of Preventative Medicine, School of Medicine, University of Colorado Health Sciences Center, Denver, CO, USA

    D W Pyatt

  3. Department of Pathology, School of Medicine, University of Colorado Health Sciences Center, Denver, CO, USA

    R D Irons

  4. Comprehensive Cancer Center, University of Colorado Health Sciences Center, Denver, CO, USA

    R D Irons

  5. Sino-US Joint Clinical and Molecular Laboratory, Fudan University, Shanghai, China

    R D Irons

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  1. J H Zheng
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  4. A T Le
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Correspondence to R D Irons.

Additional information

This project was supported by NIH Grant ES06258 to Dr Richard D Irons.

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Zheng, J., Pyatt, D., Gross, S. et al. Hydroquinone modulates the GM-CSF signaling pathway in TF-1 cells. Leukemia 18, 1296–1304 (2004). https://doi.org/10.1038/sj.leu.2403389

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