Increased p21(ras) activity in human fibroblasts transduced with survivin enhances cell proliferation

Achim Temme1, Petra Diestelkoetter-Bachert, Marc Schmitz

  • 1Institute of Immunology, Medical Faculty Carl Gustav Carus, Technical University Dresden, Fetscherstrasse 74, 01307 Dresden, Germany. temme@rcs.urz.tu-dresden.de

Insights

Overexpressing survivin in lung fibroblasts increased cell proliferation and Ras pathway activity but did not lead to cell transformation. Survivin may accelerate tumor growth by enhancing p21(Ras) activity.

Area of Science:

  • Cell Biology
  • Molecular Biology
  • Oncology

Background:

  • Survivin is crucial for mitosis and interacts with Ras GTPase-activating protein.
  • Overexpression of survivin enhances Aurora B kinase activity, an oncogenic kinase.
  • The interaction suggests a role for survivin in the Ras signaling pathway.

Purpose of the Study:

  • To investigate the role of survivin in cell proliferation and transformation.
  • To determine if survivin overexpression is sufficient for primary cell transformation.

Main Methods:

  • Overexpression of survivin in normal human lung fibroblasts.
  • Analysis of cell proliferation rates and morphology.
  • Assessment of p21(Ras) mRNA and protein expression and activation levels.
  • Soft agar colony formation assays to evaluate transformation potential.

Main Results:

  • Survivin overexpression disturbed fibroblast morphology and increased proliferation rates.
  • Elevated p21(Ras) mRNA and protein levels, along with increased activated p21(Ras), were observed.
  • Despite increased proliferation, cells remained serum-dependent and failed to form colonies in soft agar.

Conclusions:

  • Survivin overexpression enhances cell growth and p21(Ras) activity but is insufficient for primary cell transformation.
  • Survivin may contribute to tumor cell growth acceleration through its impact on the Ras pathway, beyond its anti-apoptotic function.

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