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

Mol Cell Biochem. 2004 Jan;255(1-2):19-23. doi: 10.1023/b:mcbi.0000007257.67733.3b.


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-1alpha and HIF-1beta. 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-1alpha, but not HIF-1beta, protein levels in prostate cancer cells in a mTOR-dependent manner.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Arsenites / pharmacology*
  • Aryl Hydrocarbon Receptor Nuclear Translocator
  • Cell Line, Tumor
  • DNA-Binding Proteins*
  • Enzyme Activation / drug effects
  • Humans
  • Hypoxia-Inducible Factor 1, alpha Subunit
  • Male
  • Phosphatidylinositol 3-Kinases / metabolism
  • Phosphorylation / drug effects
  • Prostatic Neoplasms / metabolism
  • Protein Kinases / metabolism
  • Receptors, Aryl Hydrocarbon / biosynthesis*
  • Ribosomal Protein S6 Kinases, 70-kDa / metabolism*
  • Signal Transduction / drug effects*
  • Sirolimus / pharmacology
  • TOR Serine-Threonine Kinases
  • Teratogens / pharmacology*
  • Transcription Factors / biosynthesis*


  • ARNT protein, human
  • Arsenites
  • DNA-Binding Proteins
  • HIF1A protein, human
  • Hypoxia-Inducible Factor 1, alpha Subunit
  • Receptors, Aryl Hydrocarbon
  • Teratogens
  • Transcription Factors
  • Aryl Hydrocarbon Receptor Nuclear Translocator
  • Protein Kinases
  • MTOR protein, human
  • Ribosomal Protein S6 Kinases, 70-kDa
  • TOR Serine-Threonine Kinases
  • ribosomal protein S6 kinase, 70kD, polypeptide 2
  • arsenite
  • Sirolimus