Abstract
Defects in cell cycle control and increased genomic instability, including gene amplification, often occur during cancer development. Cyclin D1 plays a pivotal role in G1, and this gene is frequently amplified and overexpressed in several types of human cancer. This study demonstrates that ectopic overexpression of cyclin D1 in a rat liver epithelial cell line markedly increased the yield of cells containing amplified copies of the CAD gene. This effect was associated with a loss of G1-S checkpoint control, although the cyclin D1-overexpressing cells had a normal p53 gene. The capacity of cyclin D1 to enhance gene amplification may contribute to the process of genomic instability during tumor development.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Aspartate Carbamoyltransferase / biosynthesis
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Aspartate Carbamoyltransferase / genetics*
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Carbamoyl-Phosphate Synthase (Glutamine-Hydrolyzing) / biosynthesis
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Carbamoyl-Phosphate Synthase (Glutamine-Hydrolyzing) / genetics*
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Cell Cycle / genetics*
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Cells, Cultured
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Cyclin D1
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Cyclins / biosynthesis*
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Cyclins / genetics
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Dihydroorotase / biosynthesis
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Dihydroorotase / genetics*
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Epithelial Cells
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Epithelium / metabolism
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Gene Dosage
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Gene Expression Regulation
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Humans
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Liver / metabolism*
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Multienzyme Complexes / biosynthesis
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Multienzyme Complexes / genetics*
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Oncogene Proteins / biosynthesis*
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Oncogene Proteins / genetics
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Rats
Substances
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CAD trifunctional enzyme
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Cyclins
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Multienzyme Complexes
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Oncogene Proteins
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Cyclin D1
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Aspartate Carbamoyltransferase
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Dihydroorotase
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Carbamoyl-Phosphate Synthase (Glutamine-Hydrolyzing)