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Overexpression of B-type cyclins alters chromosomal segregation

Oncogene volume 21, pages 2051–2057 (2002)Cite this article

Abstract

To identify genes which overexpression results into chromosomal instability (CIN), we developed a biological approach based on a yeast indicator strain in which CIN can be detected by a sectoring phenotype. Screening in this strain of a yeast genomic library cloned into a high copy vector led us to identify, among the clones generating 100% of sectoring colonies, Clb5, one of the six B-type cyclins present in yeast. Overexpression of cyclin B2 and cyclin B1, the two human homologs of Clb5, in the CIN indicator strain resulted also into a sectoring phenotype and induced, like overexpression of Clb5, an abnormal sensitivity to benomyl, indicating that overexpression of B-type cyclins alters the spindle checkpoint. In a series of 38 primary colorectal cancers, we detected in five tumors (13%) an accumulation of cyclin B1, which was neither related to mRNA overexpression nor to mutation within the coding region, and in five other tumors (13%) a 2–10-fold increase of cyclin B2 mRNA which was not related to gene amplification. These results suggest that overexpression of cyclins B, resulting from different mechanisms, could contribute, through an alteration of the spindle checkpoint, to the chromosomal instability observed in cancer.

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Acknowledgements

This work was supported by l'Association pour la Recherche sur le Cancer and La Fondation pour la Recherche Médicale.

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Authors and Affiliations

  1. INSERM EMI 9906, Faculté de Médecine et de Pharmacie, IFRMP, 22 boulevard Gambetta, 76183 Rouen Cedex, France

    Nasrin Sarafan-Vasseur, Aude Lamy, Jeannette Bourguignon, Richard Sesboüé, Christian Bastard, Thierry Frébourg & Jean-Michel Flaman

  2. Service d'Anatomie et Cytologie Pathologiques, Centre Hospitalo-Universitaire, 1 rue de Germont, 76031 Rouen Cedex, France

    Florence Le Pessot

  3. Centre for Molecular Medicine and Therapeutics, University of British Columbia, 950 West 28th Avenue, Vancouver, V5Z 4H4, B.C., Canada

    Philip Hieter

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  1. Nasrin Sarafan-Vasseur
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Correspondence to Thierry Frébourg.

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Sarafan-Vasseur, N., Lamy, A., Bourguignon, J. et al. Overexpression of B-type cyclins alters chromosomal segregation. Oncogene 21, 2051–2057 (2002). https://doi.org/10.1038/sj.onc.1205257

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