Gamma interferon down-regulates Fer and induces its association with inactive Stat3 in colon carcinoma cells

Oncogene. 2002 Jul 25;21(32):4997-5001. doi: 10.1038/sj.onc.1205624.

Abstract

Gamma interferon (IFN-gamma) is a regulator of cell growth, which suppresses the proliferation of HT-29 colon carcinoma cells. Here we show that in HT-29 cells IFN-gamma transiently increased the cellular level of the tyrosine kinase Fer, whose functioning was found to be essential for the proliferation of malignant cell-lines. The transient elevation in the level of Fer, was followed by its down-regulation, an effect which was most prominent after 6-8 h of IFN-gamma treatment. Up- and down-regulation of Fer was paralleled by the activation and subsequent deactivation of Stat3, which is a potent oncogene and a putative substrate of the tyrosine kinase Fer. Moreover, IFN-gamma induced the association of Fer and Stat3 and the newly formed complex was most stable at the down-regulated states of the two proteins. Formation of the Fer/Stat3 complex was accompanied by an attenuation in cell-cycle progression and accumulation of cells in the G1 phase. Thus, Fer and Stat3 are two proliferation-promoting factors whose down-regulation could contribute to the cytostatic activity of IFN-gamma in colon carcinoma cells.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antineoplastic Agents / pharmacology*
  • Cell Division / drug effects
  • Colonic Neoplasms / drug therapy
  • Colonic Neoplasms / metabolism*
  • Colonic Neoplasms / pathology
  • DNA-Binding Proteins / metabolism*
  • Down-Regulation / drug effects
  • Humans
  • Interferon-gamma / pharmacology*
  • Protein-Tyrosine Kinases
  • Proto-Oncogene Proteins / metabolism*
  • STAT3 Transcription Factor
  • Trans-Activators / metabolism*
  • Tumor Cells, Cultured

Substances

  • Antineoplastic Agents
  • DNA-Binding Proteins
  • Proto-Oncogene Proteins
  • STAT3 Transcription Factor
  • STAT3 protein, human
  • Trans-Activators
  • proto-oncogene protein c-fes-fps
  • Interferon-gamma
  • Protein-Tyrosine Kinases