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Transformation fingerprint: induced STAT3-C, v-Src and Ha-Ras cause small initial changes but similar established

Keren Paz1, Nicholas D Socci, Erik van Nimwegen

  • 1Laboratory of Molecular Cell Biology, The Rockefeller University, 1230 York Avenue, New York, NY 10021, USA.

Oncogene
|September 21, 2004
PubMed

Insights

Oncogene activation in mouse fibroblasts leads to significant mRNA changes over time. Early transcriptional alterations are subtle, but a new epigenetic state with distinct gene expression emerges during prolonged oncogenesis.

Area of Science:

  • Molecular Biology
  • Cell Biology
  • Oncogenesis

Background:

  • Oncogenic transformation involves alterations in gene expression.
  • Understanding the temporal dynamics of transcriptional changes during oncogenesis is crucial.

Purpose of the Study:

  • To investigate early and late transcriptional changes induced by oncogenes STAT3-C, v-Src, and Ha-Ras in mouse fibroblasts.
  • To compare the transcriptional profiles resulting from different oncogene activations.

Main Methods:

  • Inducible expression of oncogenes (STAT3-C, v-Src, Ha-Ras) in mouse fibroblasts using a tetracycline-repressible system.
  • DNA microarray analysis to assess global mRNA expression at 15 days post-oncogene induction.
  • RT-PCR (Reverse Transcription Polymerase Chain Reaction) to validate specific mRNA changes and analyze early transcriptional events within 24 hours.

Main Results:

  • At 15 days, DNA microarrays revealed a common set of approximately 25 elevated mRNAs across all three oncogene models.
  • Early analysis (24 hours) showed limited global transcriptional changes by microarray, except for v-Src.
  • RT-PCR detected early changes in specific genes, including STAT3-C targets like BclXI and cyclin D1, missed by microarrays.

Conclusions:

  • Early oncogene induction results in subtle or limited transcriptional alterations.
  • Prolonged oncogene expression and cell division establish a new epigenetic state characterized by a distinct transcriptional profile.
  • RT-PCR is more sensitive than microarrays for detecting early and low-abundance mRNA changes during oncogenesis.

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