Wnt inhibitory factor-1 regulates glioblastoma cell cycle and proliferation

J Clin Neurosci. 2012 Oct;19(10):1428-32. doi: 10.1016/j.jocn.2011.12.023. Epub 2012 Aug 14.


Wnt proteins are powerful regulators of cell proliferation and differentiation, and activation of the Wnt signalling pathway is involved in the pathogenesis of several types of human tumours. Wnt inhibitory factor-1 (WIF-1) acts as a Wnt antagonist and tumour suppressor. Previous studies have shown that reducing expression of the WIF-1 gene aberrantly activates Wnt signalling and induces the development of certain types of cancers. In the present study, we examined the expression of WIF-1 in human primary glioblastoma multiforme (GBM) tumours. Studies using semiquantitative reverse transcription-polymerase chain reaction and immunohistochemical analysis revealed that WIF-1 expression is lower in human GBM than in normal brain tissue. To clarify the role of WIF-1, we transfected U251 human glioblastoma-derived cells, which do not express WIF-1, with the pcDNA3.1-WIF1 vector to restore WIF-1 expression. The results of cell proliferation, colony formation and apoptosis assays, as well as flow cytometry, indicate that exogenous WIF-1 has no effect on U251 cell apoptosis, but does arrest cells at the G(0)/G(1) phase and inhibit cell growth. Collectively, our data suggest that WIF-1 is a potent inhibitor of GBM growth.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adaptor Proteins, Signal Transducing / genetics
  • Adaptor Proteins, Signal Transducing / metabolism*
  • Brain Neoplasms / physiopathology*
  • Caspase 3 / metabolism
  • Cell Cycle / physiology*
  • Cell Line, Tumor
  • Cell Proliferation
  • Chi-Square Distribution
  • Gene Expression Regulation, Neoplastic / physiology*
  • Glioblastoma / metabolism*
  • Glioblastoma / pathology
  • Glioblastoma / physiopathology*
  • Humans
  • RNA, Messenger / metabolism
  • Repressor Proteins / genetics
  • Repressor Proteins / metabolism*
  • Time Factors
  • Transfection
  • Wnt Proteins / genetics


  • Adaptor Proteins, Signal Transducing
  • RNA, Messenger
  • Repressor Proteins
  • WIF1 protein, human
  • Wnt Proteins
  • Caspase 3