Exogenous E2F expression is growth inhibitory before, during, and after cellular transformation

T. A. Lee, P. J. Farnham

Research output: Contribution to journalArticle

16 Scopus citations

Abstract

To gain insight into the tumor suppressor properties of E2F1, we investigated growth inhibition by the E2F family of transcription factors using a tissue culture model system. We first show that exogenous E2F expression causes an 80% decrease in NIH3T3 colony formation and activated c-Ha-Ras-mediated focus formation. Inhibition of Ras-mediated transformation was dependent upon E2F DNA binding activity but did not require amino- or carboxy-terminal E2F1 protein interaction domains. Because E2F upregulation has been suggested to be associated with a neoplastic phenotype, it was possible that increased E2F activity would not be inhibitory to previously transformed tells. However, we found that exogenous E2F was also inhibitory to growth of N1H3T3 cells previously transformed by Ras or Neu. Further characterization revealed that exogenous E2F expression is inhibitory at very early times after transfection, causing dramatic losses in transfected cell populations. interestingly, those few cells which do establish appear to be unaffected by the overexpressed E2F. Therefore, we propose that increased E2F activity may only be tolerated in a subset of cells which have acquired specific alterations that are dominant over E2F-mediated growth inhibition.

Original languageEnglish (US)
Pages (from-to)2257-2268
Number of pages12
JournalOncogene
Volume19
Issue number18
StatePublished - Apr 27 2000
Externally publishedYes

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Keywords

  • E2F
  • Neu
  • NIH3T3
  • Ras
  • Transformation
  • Tumor suppressor

ASJC Scopus subject areas

  • Molecular Biology
  • Cancer Research
  • Genetics

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