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Gene expression profile associated with oncogenic ras-induced senescence, cell death, and transforming properties in

Sophy S Moumtzi1, Michael L Roberts, Tobias Joyce

  • 1Laboratory of Signal Mediated Gene Expression, Institute of Biological Research and Biotechnology, National Hellenic Research Foundation, 48, Vas. Constantinou Avenue, Athens, 116 35 Greece.

Cancer Investigation
|November 4, 2009
PubMed

Insights

We created systems to study oncogenic RasV12 signaling, finding it triggers cell cycle arrest, senescence, and apoptosis. Early gene targets identified offer potential for cancer diagnostics and therapeutics.

Area of Science:

  • Molecular Biology
  • Cell Biology
  • Oncology

Background:

  • Oncogenic Ras proteins are key drivers of cancer.
  • Understanding early Ras signaling is crucial for developing targeted therapies.
  • HEK 293 cells provide a model for studying human cellular responses.

Purpose of the Study:

  • To develop inducible and constitutive expression systems for Ha-RasV12.
  • To investigate the early signaling events induced by oncogenic RasV12.
  • To identify novel Ras-target genes involved in cancer development.

Main Methods:

  • Development of inducible and constitutive Ha-RasV12 expression systems in HEK 293 cells.
  • Analysis of cellular responses including growth arrest, senescence, and apoptosis.
  • Gene expression profiling to identify early Ras-regulated genes.

Main Results:

  • Inducible RasV12 expression induced growth arrest, early senescence, and later apoptosis.
  • Early gene expression changes included proliferation (c-fos, cyclin E, cdk2), cell-cell contact (integrin a6), and signaling (MEK5, proline oxidase).
  • Ras-mediated signaling demonstrates intricate positive and negative regulation of cell cycle, senescence, and apoptosis.

Conclusions:

  • RasV12 signaling is a finely tuned process impacting multiple cellular pathways.
  • Novel early Ras-target genes were identified.
  • These genes hold potential for cancer diagnostics and therapeutic strategies.

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