Over expression of PPP2R2C inhibits human glioma cells growth through the suppression of mTOR pathway

FEBS Lett. 2013 Dec 11;587(24):3892-7. doi: 10.1016/j.febslet.2013.09.029. Epub 2013 Oct 11.

Abstract

PPP2R2C encodes a gamma isoform of the subunit B55 subfamily, which is a regulatory subunit of Protein phosphatase type 2A (PP2A). Our study shows that PPP2R2C is downregulated in glioma cells and human brain cancer patient samples. Overexpression of PPP2R2C inhibited cancer cell proliferation both in vitro and in vivo through the suppression of the activity of S6K in the mTOR pathway. Moreover, exogenous expression of PPP2R2C promoted the formation of a complex with the PP2A-C subunit to further enhance the binding of PP2A-C with S6K. Our results suggest that PPP2R2C is a potential tumor suppressor gene in human brain cancers. This study will provide novel insight into the development of therapeutic strategies in the treatment of human brain tumors.

Keywords: B55 Gamma; PPP2R2C; mTOR; p-S6K.

MeSH terms

  • Animals
  • Brain Neoplasms / genetics
  • Brain Neoplasms / pathology*
  • Cell Proliferation*
  • Down-Regulation
  • Female
  • Gene Expression Regulation, Neoplastic / physiology
  • Genes, Tumor Suppressor / physiology
  • Glioma / genetics
  • Glioma / pathology*
  • Humans
  • Mice
  • Mice, Inbred BALB C
  • Mice, Nude
  • Protein Phosphatase 2 / genetics*
  • Protein Phosphatase 2 / metabolism
  • Ribosomal Protein S6 Kinases / metabolism
  • Signal Transduction / genetics
  • TOR Serine-Threonine Kinases / genetics*
  • TOR Serine-Threonine Kinases / metabolism
  • Tumor Cells, Cultured
  • Up-Regulation / physiology

Substances

  • PPP2R2C protein, human
  • MTOR protein, human
  • Ribosomal Protein S6 Kinases
  • TOR Serine-Threonine Kinases
  • Protein Phosphatase 2