Centrosome amplification and the origin of chromosomal instability in breast cancer

Research output: Contribution to journalReview article

66 Scopus citations

Abstract

The development and progression of aggressive breast cancer is characterized by genomic instability leading to multiple genetic defects, phenotypic diversity, chemoresistance, and poor outcome. Centrosome abnormalities have been implicated in the origin of chromosomal instability through the development of multipolar mitotic spindles. Breast tumor centrosomes display characteristic structural abnormalities, termed centrosome amplification, including: increase in centrosome number and volume, accumulation of excess pericentriolar material, supernumerary centrioles, and inappropriate phosphorylation of centrosome proteins. In addition, breast tumor centrosomes also show functional abnormalities characterized by inappropriate centrosome duplication during the cell cycle and nucleation of unusually large microtubule arrays. These observations have important implications for understanding the mechanisms underlying genomic instability and loss of cell polarity in cancer. This review focuses on the coordination of the centrosome, DNA, and cell cycles in normal cells and their deregulation resulting in centrosome amplification and chromosomal instability in the development and progression of breast cancer.

Original languageEnglish (US)
Pages (from-to)275-283
Number of pages9
JournalJournal of Mammary Gland Biology and Neoplasia
Volume9
Issue number3
DOIs
StatePublished - Jul 1 2004

Keywords

  • Aneuploidy
  • Cell cycle
  • Centriole
  • Mitosis

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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