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Updated: Aug 11, 2026

Induction and Analysis of Epithelial to Mesenchymal Transition
10:37

Induction and Analysis of Epithelial to Mesenchymal Transition

Published on: August 27, 2013

Induction of transforming growth factor beta 1 resistance by the E1A oncogene requires binding to a specific set of

C Missero1, E Filvaroff, G P Dotto

  • 1Department of Pathology, Yale Medical School, New Haven, CT 06510.

Proceedings of the National Academy of Sciences of the United States of America
|April 15, 1991
PubMed

Insights

Transforming growth factor-beta (TGF-β) resistance in epithelial tumors is linked to E1A oncogene expression. E1A induces resistance by binding cellular proteins, inhibiting TGF-β signaling pathways crucial for cell growth and differentiation.

Area of Science:

  • Molecular Biology
  • Oncology
  • Cell Biology

Background:

  • Transforming growth factors beta (TGF-β) inhibit epithelial cell growth.
  • Acquiring TGF-β resistance is a key step in epithelial tumor development.

Purpose of the Study:

  • To investigate how E1A oncogene confers resistance to TGF-β growth inhibition in keratinocytes.
  • To determine the role of E1A protein interactions with cellular proteins in mediating TGF-β resistance.

Main Methods:

  • Transformation of keratinocytes with E1A or ras oncogenes.
  • Mutational analysis of E1A proteins to assess binding to retinoblastoma gene product (p105) and other proteins (p60, p107, p300).
  • Measurement of epidermal transglutaminase as a differentiation marker and TGF-β receptor levels.

Main Results:

  • E1A, but not ras, oncogene transformation induced resistance to TGF-β 1 growth inhibition.
  • E1A's ability to bind p105, p60, p107, and p300 correlated with TGF-β resistance.
  • Complete resistance was achieved when E1A mutants bound all four proteins or through combined mutants.
  • Epidermal transglutaminase induction by TGF-β was blocked in E1A-transformed cells.

Conclusions:

  • E1A induces TGF-β resistance by binding and inactivating cellular proteins downstream of the TGF-β receptor.
  • These cellular proteins are likely involved in transmitting the TGF-β growth inhibitory signal.
  • E1A's interaction with specific cellular proteins is critical for overcoming TGF-β-mediated growth arrest and maintaining a less differentiated state.

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