Abstract
Aneuploidy is a common feature of cancer cells and may contribute to cellular transformation and cancer development. In this study, we found that significant down-regulation of CDKN2A, CHEK2, CDCA8, TP53BP1, and CCNDBP1 led to chromosome imbalances in two diploid non-immortalized human cell lines; however, only CDKN2A inhibition enhanced cell proliferation and additionally up-regulated three cell cycle control genes: CDCA8, AURKA, and CCND. These results confirm that CDKN2A is a tumor suppressor gene driving human cancer development by inducing cell aneuploidy and cell cycle up-regulation.
Keywords:
Aneuploidy; CDKN2A lost; Non-immortalized normal human cells.
MeSH terms
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Aneuploidy
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Aurora Kinase A / genetics
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Cell Cycle Proteins / genetics
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Cell Line, Tumor
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Cell Proliferation / genetics*
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Cell Transformation, Neoplastic / genetics*
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Cell Transformation, Neoplastic / pathology
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Checkpoint Kinase 2 / genetics
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Cyclin-Dependent Kinase Inhibitor p16
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Cyclin-Dependent Kinase Inhibitor p18 / genetics*
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Gene Expression Regulation, Neoplastic
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Genes, Tumor Suppressor*
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Humans
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Tumor Suppressor p53-Binding Protein 1 / genetics
Substances
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CDCA8 protein, human
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CDKN2A protein, human
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Cell Cycle Proteins
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Cyclin-Dependent Kinase Inhibitor p16
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Cyclin-Dependent Kinase Inhibitor p18
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Tumor Suppressor p53-Binding Protein 1
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Checkpoint Kinase 2
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Aurora Kinase A