AURKA amplification, chromosome instability, and centrosome abnormality in human pancreatic carcinoma cells.

Published

Journal Article

To test the hypothesis that AURKA amplification contributes to pancreatic tumorigenesis by increasing centrosome abnormality and chromosome instability, the current study explored the associations between AURKA amplification, chromosome instability, centrosome abnormality, and the expression of several important proteins that are involved in cell proliferation (Ki-67), cell cycle regulation (p53, p16), and apoptosis (survivin) in 12 human pancreatic carcinoma cell lines. Using fluorescence in situ hybridization (FISH), we observed that 5 of the 12 cell lines had an AURKA amplification index (AI) (percentage of cells with more than three signals) >60%. Both the AURKA AI and the average number of signals per cell (ANSPC) were significantly associated with the copy number of chromosome 9 but not chromosome 17. The AURKA ANSPC was positively associated with the percentage of cells with the centrosome abnormality. Furthermore, centrosome abnormality was significantly associated with the frequency of cells with abnormal nuclei and abnormal mitotic figures, but no direct association was detected between the frequency of centrosome abnormalities and chromosome instabilities. The AURKA AI was also associated with a lower expression of Ki-67, a higher expression of survivin, and the lack of expression of p16. These associations support our hypothesis that AURKA amplification contributes to pancreatic carcinogenesis by increasing chromosome instability and centrosome abnormality.

Full Text

Duke Authors

Cited Authors

  • Zhu, J; Abbruzzese, JL; Izzo, J; Hittelman, WN; Li, D

Published Date

  • May 2005

Published In

Volume / Issue

  • 159 / 1

Start / End Page

  • 10 - 17

PubMed ID

  • 15860351

Pubmed Central ID

  • 15860351

International Standard Serial Number (ISSN)

  • 0165-4608

Digital Object Identifier (DOI)

  • 10.1016/j.cancergencyto.2004.09.008

Language

  • eng

Conference Location

  • United States