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Oncogenic c-H-ras deregulates survivin expression: an improvement for survival

Klaus W Sommer1, Chantal J Rodgarkia-Dara, Claudia Schreiner

  • 1Clinics of Internal Medicine I, Division Institute of Cancer Research, Medical University of Vienna, Borschkegasse 8a, 1090 Vienna, Austria.

FEBS Letters
|October 2, 2007
PubMed

Insights

Oncogenic c-H-ras sustains survivin protein expression throughout the cell cycle, protecting cells from apoptosis. Survivin silencing reversed this anti-apoptotic effect, linking its function to c-H-ras activity.

Area of Science:

  • Molecular Biology
  • Cell Biology
  • Cancer Research

Background:

  • Survivin is a key protein regulating cell division and apoptosis.
  • Survivin expression is typically confined to the G2/M phase of the cell cycle.
  • Survivin plays a role in protecting cells from apoptosis.

Purpose of the Study:

  • To investigate the relationship between oncogenic c-H-ras and survivin expression.
  • To determine if c-H-ras influences survivin's cell cycle regulation and anti-apoptotic function.
  • To link survivin's anti-apoptotic properties to its cell cycle regulation by c-H-ras.

Main Methods:

  • Overexpression of constitutively active c-H-ras in HeLa cells.
  • Induction of c-H-ras in a stable HeLaDiR cell line.
  • siRNA-mediated silencing of survivin.

Main Results:

  • Sustained survivin expression in all cell cycle phases upon c-H-ras activation.
  • Protection of cells from drug-induced apoptosis by sustained survivin expression.
  • Reversal of this protective effect upon survivin silencing.

Conclusions:

  • Oncogenic c-H-ras drives sustained survivin expression independent of the normal cell cycle.
  • Survivin's anti-apoptotic function is linked to its cell cycle-independent regulation by oncogenic c-H-ras.
  • This interaction provides a potential therapeutic target in cancer.

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