Suppression of polyploidy by the BRCA2 protein.
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.
Sagulenko
Evgeny
E
Department of Tumor Genetics B030, German Cancer Research Centre, Im Neuenheimer Feld 280, 69120 Heidelberg, Germany. e.sagulenko@dkfz.de
Savelyeva
Larissa
L
Ehemann
Volker
V
Sagulenko
Vitaliya
V
Hofmann
Wera
W
Arnold
Katrin
K
Claas
Andreas
A
Scherneck
Siegfried
S
Schwab
Manfred
M
D000483:Alleles; D051017:Apoptosis Regulatory Proteins; D064107:Aurora Kinase B; D064127:Aurora Kinases; D024682:BRCA2 Protein / Q000235:genetics* / Q000502:physiology*; D001943:Breast Neoplasms / Q000235:genetics* / Q000378:metabolism* / Q000473:pathology; D002453:Cell Cycle; D002467:Cell Nucleus / Q000378:metabolism; D050759:Cyclin-Dependent Kinase Inhibitor p21 / Q000378:metabolism; D050687:E2F1 Transcription Factor / Q000378:metabolism; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D009711:Nucleotides / Q000737:chemistry; D011123:Polyploidy; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism; D016160:Retinoblastoma Protein / Q000378:metabolism
D051017:Apoptosis Regulatory Proteins; C118024:BLID protein, human; D024682:BRCA2 Protein; C551750:BRCA2 protein, human; D050759:Cyclin-Dependent Kinase Inhibitor p21; D050687:E2F1 Transcription Factor; C493753:E2F1 protein, human; D009711:Nucleotides; D016160:Retinoblastoma Protein; C576921:AURKB protein, human; D064107:Aurora Kinase B; D064127:Aurora Kinases; D017346:Protein Serine-Threonine Kinases