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
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Research Support, Non-U.S. Gov't
MeSH terms
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Alleles
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Apoptosis Regulatory Proteins
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Aurora Kinase B
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Aurora Kinases
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BRCA2 Protein / genetics*
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BRCA2 Protein / physiology*
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Breast Neoplasms / genetics*
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Breast Neoplasms / metabolism*
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Breast Neoplasms / pathology
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Cell Cycle
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Cell Nucleus / metabolism
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Cyclin-Dependent Kinase Inhibitor p21 / metabolism
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E2F1 Transcription Factor / metabolism
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Gene Expression Regulation, Neoplastic*
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Humans
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In Situ Hybridization, Fluorescence
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Nucleotides / chemistry
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Polyploidy*
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Protein Serine-Threonine Kinases / metabolism
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Retinoblastoma Protein / metabolism
Substances
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Apoptosis Regulatory Proteins
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BLID protein, human
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BRCA2 Protein
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BRCA2 protein, human
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Cyclin-Dependent Kinase Inhibitor p21
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E2F1 Transcription Factor
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E2F1 protein, human
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Nucleotides
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Retinoblastoma Protein
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AURKB protein, human
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Aurora Kinase B
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Aurora Kinases
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Protein Serine-Threonine Kinases