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

Patrick E. Carroll, Masaru Okuda, Henning Horn, Paul Biddinger, Peter J. Stambrook, Lyon L. Gleich, Ya Qin Li, Pheruza Tarapore, Kenji Fukasawa

Research output: Contribution to journalArticle

208 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)1935-1944
Number of pages10
JournalOncogene
Volume18
Issue number11
Publication statusPublished - 18 Mar 1999
Externally publishedYes

Fingerprint

Centrosome
Chromosomal Instability
Human Chromosomes
Mutation
Neoplasms
Tumor Suppressor Protein p53
Loss of Heterozygosity
Mitosis
Squamous Cell Carcinoma
Cultured Cells
Breast

Keywords

  • Centrosome hyperamplification
  • Chromosome instability
  • Human cancer
  • Mdm2
  • p53

ASJC Scopus subject areas

  • Molecular Biology
  • Cancer Research
  • Genetics

Cite this

Carroll, P. E., Okuda, M., Horn, H., Biddinger, P., Stambrook, P. J., Gleich, L. L., ... Fukasawa, K. (1999). Centrosome hyperamplification in human cancer: Chromosome instability induced by p53 mutation and/or Mdm2 overexpression. Oncogene, 18(11), 1935-1944.

Centrosome hyperamplification in human cancer : Chromosome instability induced by p53 mutation and/or Mdm2 overexpression. / Carroll, Patrick E.; Okuda, Masaru; Horn, Henning; Biddinger, Paul; Stambrook, Peter J.; Gleich, Lyon L.; Li, Ya Qin; Tarapore, Pheruza; Fukasawa, Kenji.

In: Oncogene, Vol. 18, No. 11, 18.03.1999, p. 1935-1944.

Research output: Contribution to journalArticle

Carroll, PE, Okuda, M, Horn, H, Biddinger, P, Stambrook, PJ, Gleich, LL, Li, YQ, Tarapore, P & Fukasawa, K 1999, 'Centrosome hyperamplification in human cancer: Chromosome instability induced by p53 mutation and/or Mdm2 overexpression', Oncogene, vol. 18, no. 11, pp. 1935-1944.
Carroll PE, Okuda M, Horn H, Biddinger P, Stambrook PJ, Gleich LL et al. Centrosome hyperamplification in human cancer: Chromosome instability induced by p53 mutation and/or Mdm2 overexpression. Oncogene. 1999 Mar 18;18(11):1935-1944.
Carroll, Patrick E. ; Okuda, Masaru ; Horn, Henning ; Biddinger, Paul ; Stambrook, Peter J. ; Gleich, Lyon L. ; Li, Ya Qin ; Tarapore, Pheruza ; Fukasawa, Kenji. / Centrosome hyperamplification in human cancer : Chromosome instability induced by p53 mutation and/or Mdm2 overexpression. In: Oncogene. 1999 ; Vol. 18, No. 11. pp. 1935-1944.
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