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Centrosome hyperamplification in human cancer: chromosome instability induced by p53 mutation and/or Mdm2 overexpression

Oncogene volume 18, pages 1935–1944 (1999)Cite this article

Abstract

We have previously reported that loss of p53 tumor suppressor protein results in centrosome hyperamplification, which leads to aberrant mitosis and chromosome instability. Since p53 is either deleted or mutated in human cancers at a high frequency, we investigated whether human cancers showed centrosome hyperamplification. Screening of advanced stage breast ductal carcinomas and squamous cell carcinomas of the head and neck (SCCHN) revealed that centrosome hyperamplification is frequent in both tumor types. Moreover, through the analyses of p53 in SCCHN samples by direct sequencing and by loss-of-heterozygosity test, we found that p53 mutations correlated with occurrence of centrosome hyperamplification. However, in some cases, we observed centrosome hyperamplification in tumors that retained wild-type p53. These tumors contained high levels of Mdm2. Since Mdm2 can inactivate p53 through physical association, we investigated whether Mdm2 overexpression induced centrosome hyperamplification. We found that Mdm2 overexpression, like loss of p53, induced centrosome hyperamplification and chromosome instability in cultured cells.

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Acknowledgements

We thank Drs M Oren (Weizmann Institute) for mouse Mdm2 plasmids and D George (University of Pennsylvania) for human Mdm2 plasmids. We also thank Dr S Berberich (Wright State University) for helpful discussions. This work was supported by a grant from American Cancer Society.

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Authors and Affiliations

  1. Department of Cell Biology, University of Cincinnati College of Medicine, PO Box 670521, Cincinnati, 45267-0521, Ohio, USA

    Patrick E Carroll, Masaru Okuda, Henning F Horn, Peter J Stambrook, Pheruza Tarapore & Kenji Fukasawa

  2. Department of Pathology and Laboratory Medicine, University of Cincinnati College of Medicine, PO Box 670521, Cincinnati, 45267-0521, Ohio, USA

    Paul Biddinger

  3. Department of Otolaryngology, University of Cincinnati College of Medicine, PO Box 670521, Cincinnati, 45267-0521, Ohio, USA

    Lyon L Gleich & Ya-Qin Li

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Carroll, P., Okuda, M., Horn, H. et al. Centrosome hyperamplification in human cancer: chromosome instability induced by p53 mutation and/or Mdm2 overexpression. Oncogene 18, 1935–1944 (1999). https://doi.org/10.1038/sj.onc.1202515

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