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Spatio-Temporal Manipulation of Small GTPase Activity at Subcellular Level and on Timescale of Seconds in Living Cells
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Spatio-Temporal Manipulation of Small GTPase Activity at Subcellular Level and on Timescale of Seconds in Living Cells

Published on: March 9, 2012

AP-1 complexes containing cJun and JunB cause cellular transformation of Rat1a fibroblasts and share transcriptional

Virna D Leaner1, Ichiro Kinoshita, Michael J Birrer

  • 1Cell and Cancer Biology Department, National Cancer Institute, National Institutes of Health, Rockville, MD 20850, USA.

Oncogene
|August 29, 2003
PubMed

Insights

Jun proteins cJun and JunB promote cell transformation and anchorage-independent growth, while JunD inhibits proliferation. This study identifies specific genes linked to transformation, distinguishing them from bystander genes.

Area of Science:

  • Molecular Biology
  • Cell Biology
  • Oncology

Background:

  • The Jun proteins (cJun, JunB, JunD) are transcription factors that form Activator Protein-1 (AP-1) complexes.
  • AP-1 regulates genes involved in cell proliferation, differentiation, and survival.
  • The distinct roles of individual Jun proteins in cell transformation are not fully understood.

Purpose of the Study:

  • To investigate the specific roles of cJun, JunB, and JunD in fibroblast cell growth and transformation.
  • To identify genes regulated by cJun and JunB that contribute to anchorage-independent growth.
  • To differentiate transformation-related genes from bystander genes regulated by AP-1.

Main Methods:

  • Utilized a doxycycline-inducible retroviral vector to control Jun protein expression in rat fibroblasts.
  • Employed Affymetrix Rat oligonucleotide microarrays (RG_U34A) for differential gene expression analysis.
  • Validated gene expression changes using Northern blot analysis.

Main Results:

  • AP-1 complexes with cJun and JunB induced morphological alterations and anchorage-independent growth.
  • AP-1 complexes with JunD exhibited an antiproliferative effect.
  • Identified 33 candidate genes differentially regulated by cJun and JunB but not JunD, involved in metabolism, growth, signaling, migration, and adhesion.
  • Validated 10 genes, with 8 confirmed as potential direct AP-1 targets.

Conclusions:

  • Inducible expression of cJun and JunB drives anchorage-independent growth in Rat1a cells, distinct from JunD.
  • A functional genomics approach effectively distinguishes transformation-specific AP-1 target genes from bystander genes.
  • This model system facilitates the targeted identification of genes critical for cellular transformation.

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