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Absence of p21WAF1 cooperates with c-myc in bypassing Ras-induced senescence and enhances oncogenic cooperation

Oncogene volume 23, pages 6006–6011 (2004)Cite this article

Abstract

The absence of p21waf1 combined with an ectopic expression of c-myc prevents ras-induced senescence in mouse embryo fibroblasts. Extension of lifespan after c-myc transduction into p21-null cells was followed at later passages by apoptosis of a large fraction of c-myc-overexpressing p21-null cells. This apoptotic effect could be overridden by inactivation of the p53 tumor suppressor or oncogenic ras expression. Ras-induced inhibition of apoptosis is mediated by PI3K activation. These results suggest a functional relationship between ras and myc that may explain their oncogenic cooperation. The number of foci formed by myc+ras increased cooperatively in the absence of p21waf1. Thus, the reciprocal cooperation between myc and ras in a p21-null background during cellular immortalization lead to increased oncogenic cooperation between ras and myc.

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Acknowledgements

This work has been funded by Cancer Research Campaign UK (CRC #SP 2366/0201) and Ministerio de Ciencia y Tecnologia (BIO2001-0069). DHB is funded by the Hugh and Catherine Stevenson Chair.

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  1. Experimental Therapeutics Programme, Centro Nacional de Investigaciones Oncológicas (CNIO), Madrid, Spain

    Amancio Carnero

  2. Wolfson Institute for Biomedical Research, UCL, Cruciform Building, Gower Street, London, WC1E 6BT, UK

    David H Beach

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  1. Amancio Carnero
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  2. David H Beach
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Correspondence to Amancio Carnero.

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Carnero, A., Beach, D. Absence of p21WAF1 cooperates with c-myc in bypassing Ras-induced senescence and enhances oncogenic cooperation. Oncogene 23, 6006–6011 (2004). https://doi.org/10.1038/sj.onc.1207839

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