Molecular and Cellular Biochemistry

, Volume 255, Issue 1–2, pp 19–23

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

  • Heath D. Skinner
  • Xiao-song Zhong
  • Ning Gao
  • Xianglin Shi
  • Bing-Hua Jiang
Article

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.

arsenite HIF-1 p70S6K1 PI3K mTOR 

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Copyright information

© Kluwer Academic Publishers 2004

Authors and Affiliations

  • Heath D. Skinner
    • 1
  • Xiao-song Zhong
    • 1
  • Ning Gao
    • 1
  • Xianglin Shi
    • 2
  • Bing-Hua Jiang
    • 1
  1. 1.Mary Babb Randolph Cancer Center, Department of Microbiology, Immunology and Cell BiologyWest Virginia UniversityMorgantownUSA
  2. 2.Health Effects Laboratory DivisionNational Institute for Occupational Safety and HealthMorgantownUSA

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