Suppression of polyploidy by the BRCA2 protein

Cancer Lett. 2007 Nov 8;257(1):65-72. doi: 10.1016/j.canlet.2007.07.003. Epub 2007 Aug 7.

Abstract

Mounting evidence implicates BRCA2 not only in maintenance of genome integrity but also in cell-cycle checkpoints. However, the contribution of BRCA2 in the checkpoints is still far from being understood. Here, we demonstrate that breast cancer cells MX-1 are unable to maintain genome integrity, which results in gross polyploidization. We generated MX-1 clones, stably expressing BRCA2, and found that BRCA2 acts to suppress polyploidy. Compared with MX-1, the ectopically BRCA2-expressing cells had different intracellular levels of Aurora A, Aurora B, p21, E2F-1, and pRb, suggesting a BRCA2-mediated suppression of polyploidy via stabilization of the checkpoint proteins levels.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alleles
  • Apoptosis Regulatory Proteins
  • Aurora Kinase B
  • Aurora Kinases
  • BRCA2 Protein / genetics*
  • BRCA2 Protein / physiology*
  • Breast Neoplasms / genetics*
  • Breast Neoplasms / metabolism*
  • Breast Neoplasms / pathology
  • Cell Cycle
  • Cell Nucleus / metabolism
  • Cyclin-Dependent Kinase Inhibitor p21 / metabolism
  • E2F1 Transcription Factor / metabolism
  • Gene Expression Regulation, Neoplastic*
  • Humans
  • In Situ Hybridization, Fluorescence
  • Nucleotides / chemistry
  • Polyploidy*
  • Protein Serine-Threonine Kinases / metabolism
  • Retinoblastoma Protein / metabolism

Substances

  • Apoptosis Regulatory Proteins
  • BLID protein, human
  • BRCA2 Protein
  • BRCA2 protein, human
  • Cyclin-Dependent Kinase Inhibitor p21
  • E2F1 Transcription Factor
  • E2F1 protein, human
  • Nucleotides
  • Retinoblastoma Protein
  • AURKB protein, human
  • Aurora Kinase B
  • Aurora Kinases
  • Protein Serine-Threonine Kinases