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

Oncogene volume 19, pages 2257–2268 (2000)Cite this article

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 cells. However, we found that exogenous E2F was also inhibitory to growth of NIH3T3 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.

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Acknowledgements

We are grateful to Richard Burgess, Doug Cress, LW Enquist, Doron Ginsberg, Michael Gould, Ed Harlow, Kristen Helin, Wilhelm Krek, Jackie Lees, David Livingston, Joseph Nevins, Bill Sugden and Phillip Watson for providing plasmids and reagents and to Kathy Schell and Kristen Elmer for assistance with flow cytometry. We also thank members of the Farnham laboratory for critical readings of this manuscript. This work was supported in part by Public Health Service Grants CA07175, CA22484 and predoctoral training grants CA09135 and DAMD17-96-1-6109.

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  1. Department of Oncology, McArdle Laboratory for Cancer Research, University of Wisconsin Medical School, Madison, 53706, Wisconsin, WI, USA

    T A Lee & P J Farnham

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Lee, T., Farnham, P. Exogenous E2F expression is growth inhibitory before, during, and after cellular transformation. Oncogene 19, 2257–2268 (2000). https://doi.org/10.1038/sj.onc.1203556

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