Up-regulation of gut-enriched krüppel-like factor by interferon-gamma in human colon carcinoma cells

Z Y Chen1, J Shie, C Tseng

  • 1Section of Gastroenterology, Boston VA Medical Center and Boston University School of Medicine, E.R.B.C. Room 513, 650 Albany Street, 02118, Boston, MA, USA.

FEBS Letters
|July 19, 2000
PubMed

Insights

Interferon-gamma (IFN-gamma) triggers tumor cell death and growth arrest by upregulating gut-enriched krüppel-like factor (GKLF). GKLF acts as a key downstream mediator of IFN-gamma's anti-cancer effects.

Area of Science:

  • Oncology
  • Molecular Biology
  • Cell Biology

Background:

  • Interferon-gamma (IFN-gamma) is known to induce tumor cell apoptosis and growth arrest.
  • The precise molecular mechanisms underlying these effects remain largely unknown.
  • Gut-enriched krüppel-like factor (GKLF) has recently emerged with similar anti-tumorigenic properties.

Purpose of the Study:

  • To investigate the relationship between IFN-gamma treatment and GKLF expression in tumor cells.
  • To elucidate the role of GKLF as a potential downstream mediator of IFN-gamma's anti-cancer functions.
  • To understand the kinetics and regulatory pathways of GKLF induction by IFN-gamma.

Main Methods:

  • Treatment of HT-29 colon cancer cells with varying doses and durations of IFN-gamma.
  • Analysis of cell proliferation and apoptosis assays.
  • Quantitative assessment of GKLF mRNA and protein levels.
  • Investigation of p53 independence and requirement for de novo protein synthesis.
  • Overexpression studies of GKLF.

Main Results:

  • IFN-gamma treatment significantly inhibited HT-29 cell proliferation and induced apoptosis.
  • These effects were strongly associated with increased GKLF expression.
  • IFN-gamma upregulated GKLF mRNA and protein in a dose- and time-dependent manner.
  • GKLF induction was rapid, independent of p53, and did not require new protein synthesis, classifying it as an immediate-early gene.
  • Overexpression of GKLF mimicked the anti-proliferative and pro-apoptotic effects of IFN-gamma.

Conclusions:

  • Gut-enriched krüppel-like factor (GKLF) is a critical downstream target of Interferon-gamma (IFN-gamma) in tumor cells.
  • GKLF mediates the anti-proliferative and pro-apoptotic effects of IFN-gamma, suggesting its role in cancer therapy.
  • The rapid, p53-independent induction of GKLF highlights its significance as an immediate-early response gene to IFN-gamma.

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