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[Cancer Research 62, 3511-3514, June 15, 2002]
© 2002 American Association for Cancer Research

Molecular Biology and Genetics

Deregulated DNA Polymerase ß Induces Chromosome Instability and Tumorigenesis1

Valérie Bergoglio, Marie-Jeanne Pillaire, Magali Lacroix-Triki, Brigitte Raynaud-Messina, Yvan Canitrot, Anne Bieth, Michèle Garès, Michel Wright, Georges Delsol, Lawrence A. Loeb, Christophe Cazaux and Jean-Sébastien Hoffmann2

Group "Instabilité génétique et cancer" [V. B., M-J. P., Y. C., A. B., C. C., J-S. H.] and Group "Pharmacologie et dynamique du cytosquelette microtubulaire" [B. R-M., M. G., M. W.], Institut de Pharmacologie et de Biologie Structurale, CNRS UPR 9062, 31077 Toulouse, cedex 4, France; ARECA network-Histopathology Experimental Platform, CHU Purpan, 31059 Toulouse, France [M. L-T., G. D.]; and The Joseph Gottstein Memorial Cancer Laboratory, Department of Pathology, University of Washington School of Medicine, Seattle, Washington 98195-7705 [L. A. L.]

To reach the biological alterations that characterize cancer, the genome of tumor cells must acquire increased mutability resulting from a malfunction of a network of genome stability systems, e.g., cell cycle arrest, DNA repair, and high accuracy of DNA synthesis during DNA replication. Numeric chromosomal imbalance, referred to as aneuploidy, is the most prevalent genetic changes recorded among many types of solid tumors. We report here that ectopic expression in cells of DNA polymerase ß, an error-prone enzyme frequently over-regulated in human tumors, induces aneuploidy, an abnormal localization of the centrosome-associated {gamma}-tubulin protein during mitosis, a deficient mitotic checkpoint, and promotes tumorigenesis in nude immunodeficient mice. Thus, we find that alteration of polymerase ß expression appears to induce major genetic changes associated with a malignant phenotype.




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Copyright © 2002 by the American Association for Cancer Research.