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Loss of LIN9, a member of the DREAM complex, cooperates with SV40 large T antigen to induce genomic instability and anchorage-independent growth

Oncogene volume 31, pages 1859–1868 (2012)Cite this article

Abstract

The DREAM complex is an important regulator of mitotic gene expression during the cell cycle. Here we report that inactivation of LIN9, a subunit of DREAM, results in premature senescence, which can be overcome by the SV40 large T (LT) antigen. Together with the observation that p16INK4a and p21Waf1 are upregulated upon loss of LIN9, these results indicate that senescence is triggered by the pRB and p53 tumor suppressor pathways. We also find that LIN9-null cells that escape senescence are chromosomally instable because of compromised mitotic fidelity. SV40 LT-expressing cells that adapt to the loss of LIN9 can grow anchorage-independently in soft agar, a hallmark of oncogenic transformation. Taken together, these results suggest an important role of mitotic gene regulation in the maintenance of genomic stability and tumor suppression.

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Acknowledgements

We thank all members of the laboratory for their suggestions and critical reading of the manuscript. We also thank Michael Schmid and Claus Steinlein for their advice and help with karyotype analysis. This work was supported by grants from the DFG (575/6-1 and TR17-B1) to SG.

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Author notes

  1. N Reichert

    Present address: 3Current address: Friedrich Miescher Institute for Biomedical Research, Novartis Research Foundation, Basel, Switzerland.,

  2. S Hauser and T Ulrich: These authors contributed equally to this work.

Authors and Affiliations

  1. Department of Physiological Chemistry I, Biocenter, University of Wuerzburg, Wuerzburg, Germany

    S Hauser, T Ulrich, S Wurster, K Schmitt, N Reichert & S Gaubatz

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  1. S Hauser
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Correspondence to S Gaubatz.

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Hauser, S., Ulrich, T., Wurster, S. et al. Loss of LIN9, a member of the DREAM complex, cooperates with SV40 large T antigen to induce genomic instability and anchorage-independent growth. Oncogene 31, 1859–1868 (2012). https://doi.org/10.1038/onc.2011.364

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