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


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

1999-03

AUTHORS

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

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. More... »

PAGES

1935

Identifiers

URI

http://scigraph.springernature.com/pub.10.1038/sj.onc.1202515

DOI

http://dx.doi.org/10.1038/sj.onc.1202515

DIMENSIONS

https://app.dimensions.ai/details/publication/pub.1041442693

PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/10208415


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