Overexpression of cyclin D1 enhances gene amplification.
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.
Department of Pharmacology, Columbia-Presbyterian Cancer Center, New York, New York 10032, USA.
P
P
Zhou
W
W
Jiang
C M
CM
Weghorst
I B
IB
Weinstein
D000818:Animals; D001221:Aspartate Carbamoyltransferase / Q000096:biosynthesis / Q000235:genetics*; D002223:Carbamoyl-Phosphate Synthase (Glutamine-Hydrolyzing) / Q000096:biosynthesis / Q000235:genetics*; D002453:Cell Cycle / Q000235:genetics*; D002478:Cells, Cultured; D019938:Cyclin D1; D016213:Cyclins / Q000096:biosynthesis* / Q000235:genetics; D004080:Dihydroorotase / Q000096:biosynthesis / Q000235:genetics*; D004847:Epithelial Cells; D004848:Epithelium / Q000378:metabolism; D018628:Gene Dosage; D005786:Gene Expression Regulation; D006801:Humans; D008099:Liver / Q000378:metabolism*; D009097:Multienzyme Complexes / Q000096:biosynthesis / Q000235:genetics*; D015513:Oncogene Proteins / Q000096:biosynthesis* / Q000235:genetics; D051381:Rats
C033626:CAD trifunctional enzyme; D016213:Cyclins; D009097:Multienzyme Complexes; D015513:Oncogene Proteins; D019938:Cyclin D1; D001221:Aspartate Carbamoyltransferase; D004080:Dihydroorotase; D002223:Carbamoyl-Phosphate Synthase (Glutamine-Hydrolyzing)