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Driving the Cell Cycle to Cancer

  • Chapter
New Trends in Cancer for the 21st Century

Part of the book series: Advances in Experimental Medicine and Biology ((AEMB,volume 532))

Abstract

Cell cycle progression requires the co-ordinated activation of several kinases, some of which are activated upon the binding of a cyclin subunit. At least four of these so-called cyclin-dependent kinases, namely Cdk4, Cdk6, Cdk2 and Cdkl, have specific roles at particular stages of the cell cycle, including passage through the various cell cycle transitions and the response to specific checkpoints. Not surprisingly, most human tumors carry mutations that deregulate at least one of these kinases. To analyze their specific role in vivo, we are generating strains of gene-targeted mice carrying either activated or defective alleles of these Cdks. As an example, Cdk4 expression appears to be expendable in most cell types since mice lacking Cdk4 are viable. Yet, Cdk4 mutant mice are smaller in size and infertile (only partial infertility in males). In addition, Cdk4 defective mice develop insulin dependent diabetes early in life. However, the importance of these Cdks in tumor cell cycles is underscored by the phenotype of knock in mice where the normal Cdk4 gene has been replaced by a Cdk4 R24C (insensitive to INK inhibitors) mutant. These animals develop a wide spectrum of spontaneous tumors and are highly susceptible to specific carcinogenic treatments. These models are being used now to understand how deregulation of these Cdks leads to cancer development and will be a valuable tool to design and validate new therapeutic strategies against tumour development.

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Author information

Authors and Affiliations

  1. Molecular Oncology Progamme, Centro Nacional de Investigaciones Oncológicas, Madrid, Spain

    Marcos Malumbres, Sarah L. Hunt, Rocío Sotillo, Javier Martín, Jun Odajima, Alberto Martín, Sagrario Ortega & Mariano Barbacid

  2. University of Bourdeaux, Bourdeaux, France

    Pierre Dubus

Authors
  1. Marcos Malumbres
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  2. Sarah L. Hunt
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  3. Rocío Sotillo
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  4. Javier Martín
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  5. Jun Odajima
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  6. Alberto Martín
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  7. Pierre Dubus
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  8. Sagrario Ortega
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  9. Mariano Barbacid
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Corresponding author

Correspondence to Marcos Malumbres .

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Editors and Affiliations

  1. University of Valencia, Valencia, Spain

    Antonio Llombart-Bosch

  2. Valencian Foundation for Biomedical Research, Valencia, Spain

    Vicente Felipo

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© 2003 Springer Science+Business Media New York

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Malumbres, M. et al. (2003). Driving the Cell Cycle to Cancer. In: Llombart-Bosch, A., Felipo, V. (eds) New Trends in Cancer for the 21st Century. Advances in Experimental Medicine and Biology, vol 532. Springer, Boston, MA. https://doi.org/10.1007/978-1-4615-0081-0_1

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  • DOI: https://doi.org/10.1007/978-1-4615-0081-0_1

  • Publisher Name: Springer, Boston, MA

  • Print ISBN: 978-1-4613-4914-3

  • Online ISBN: 978-1-4615-0081-0

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