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Evidence for a function of CtBP in epithelial gene regulation and anoikis

Oncogene volume 19, pages 3823–3828 (2000)Cite this article

Abstract

Previously, we reported that adenovirus E1a protein behaves as a tumor suppressor in human cells. It apparently functions by transcriptionally inducing an array of epithelial cell adhesion genes, while repressing other cell-type specific genes, thus producing an epithelial phenotype. Concomitantly, the cells become sensitive to anoikis (apoptosis of epithelial cells detached from extracellular matrix), potentially causing tumor suppression. E1a protein interacts with the nuclear acetylases p300, CBP and P/CAF, and also with the co-repressor protein CtBP. In this study, we have determined the role of these interactions in E1a's phenotypic effects on human tumor cells. The results indicate that E1a's interaction with CtBP activates at least three epithelial cell adhesion gene promoters. The E-cadherin repressor appeared to be the CtBP-interacting protein δ EF1/ZEB, which bound the ras-repressible E-boxes of the E-cadherin promoter. The E1a–CtBP interaction also contributed to anoikis-sensitization. E1a's interactions with the nuclear acetylases conferred epithelial morphologies but did not activate epithelial genes. These latter interactions did not sensitize tumor cells to anoikis but nevertheless conferred tumor suppression. These results implicate CtBP as an antagonist of the epithelial phenotype and anoikis. They also indicate a new but undefined role for nuclear acetylases in maintaining the transformed phenotype.

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Acknowledgements

We wish to thank Derek Kelaita for technical assistance, Tony Kouzarides, Douglas Dean and Hisato Kondoh for providing crucial reagents. The work was partially supported by an IDEA award from the University of California and by Targeted Genetics Corp.

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  1. The Burnham Institute, 10901 N, Torrey Pines Road, La Jolla, 92037, California, CA, USA

    Madeleine L Grooteclaes & Steven M Frisch

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  1. Madeleine L Grooteclaes
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  2. Steven M Frisch
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Grooteclaes, M., Frisch, S. Evidence for a function of CtBP in epithelial gene regulation and anoikis. Oncogene 19, 3823–3828 (2000). https://doi.org/10.1038/sj.onc.1203721

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