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14-3-3gamma induces oncogenic transformation by stimulating MAP kinase and PI3K signaling

Vijayababu M Radhakrishnan1, Jesse D Martinez

  • 1Arizona Cancer Center, Department of Cell Biology and Anatomy, University of Arizona, Tucson, Arizona, United States of America.

Plos One
|July 15, 2010
PubMed

Insights

14-3-3gamma acts as an oncogene, promoting cell transformation and tumor formation. This protein activates MAP kinase and PI3K signaling pathways, crucial for its oncogenic activity.

Area of Science:

  • Cellular Biology
  • Molecular Oncology
  • Signal Transduction

Background:

  • 14-3-3 proteins are conserved scaffolding proteins regulating critical cellular processes.
  • Elevated expression of some 14-3-3 family members is observed in human cancers, suggesting a role in tumorigenesis.

Purpose of the Study:

  • To investigate the oncogenic potential of 14-3-3gamma.
  • To elucidate the role of 14-3-3sigma as a potential tumor suppressor.
  • To identify the signaling pathways involved in 14-3-3gamma-mediated transformation.

Main Methods:

  • Transfection of NIH3T3 mouse fibroblast cells with 14-3-3gamma.
  • Focus formation and tumor formation assays in SCID mice.
  • Analysis of MAP kinase (MAPK) and phosphatidylinositol 3-kinase (PI3K) signaling pathways.
  • Co-immunoprecipitation to study protein interactions.

Main Results:

  • 14-3-3gamma transfection induced focus and tumor formation in NIH3T3 cells.
  • 14-3-3sigma inhibited NIH3T3 cell transformation induced by H-ras and c-myc.
  • Activation of both MAPK and PI3K signaling pathways was essential for 14-3-3gamma-induced transformation.
  • 14-3-3gamma was found to interact with PI3K and TSC2, suggesting a role in stimulating PI3K signaling.

Conclusions:

  • 14-3-3gamma functions as an oncogene.
  • MAPK and PI3K signaling pathways are critical for 14-3-3gamma-induced cellular transformation.
  • 14-3-3gamma may promote tumorigenesis by activating these key signaling pathways.

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