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Arsenite induces p70S6K1 activation and HIF-1α expression in prostate cancer cells

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Abstract

Arsenite is ubiquitous in the environment, particularly in the form of contaminated water. Although this metal is a known human carcinogen, its exact mechanism of action remains unclear. P70S6K1 phosphorylates the ribosomal 40S protein leading to increased protein translation, and is an important regulator of cell growth and proliferation. Hypoxia inducible factor-1 (HIF-1) is a basic helix-loop-helix transcription factor composed of two subunits, HIF-1α and HIF-1β. HIF-1 activates the transcription of a number of genes that mediate angiogenesis and tumor formation. In this study we demonstrated that arsenite treatment increased levels of p70S6K1 phosphorylation and p70S6K1 activity in a PI3K and mTOR sensitive manner. We have also shown that arsenite specifically induces HIF-1α, but not HIF-1β, protein levels in prostate cancer cells in a mTOR-dependent manner.

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Authors and Affiliations

  1. Mary Babb Randolph Cancer Center, Department of Microbiology, Immunology and Cell Biology, West Virginia University, Morgantown, WV, 26505-9300, USA

    Heath D. Skinner, Xiao-song Zhong, Ning Gao & Bing-Hua Jiang

  2. Health Effects Laboratory Division, National Institute for Occupational Safety and Health, Morgantown, WV, 26505, USA

    Xianglin Shi

Authors
  1. Heath D. Skinner
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  2. Xiao-song Zhong
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  3. Ning Gao
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  4. Xianglin Shi
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  5. Bing-Hua Jiang
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Skinner, H.D., Zhong, Xs., Gao, N. et al. Arsenite induces p70S6K1 activation and HIF-1α expression in prostate cancer cells. Mol Cell Biochem 255, 19–23 (2004). https://doi.org/10.1023/B:MCBI.0000007257.67733.3b

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  • DOI: https://doi.org/10.1023/B:MCBI.0000007257.67733.3b

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