Defects in cell cycle control and increased genomic instability, inclu
ding gene amplification, often occur during cancer development. Cyclin
D1 plays a pivotal role in G(1), and this gene is frequently amplifie
d and overexpressed in several types of human cancer. This study demon
strates that ectopic overexpression of cyclin D1 in a rat liver epithe
lial cell line markedly increased the yield of cells containing amplif
ied copies of the CAD gene. This effect was associated with a loss of
G(1)-S checkpoint control, although the cyclin D1-overexpressing cells
had a normal p53 gene. The capacity of cyclin D1 to enhance gene ampl
ification may contribute to the process of genomic instability during
tumor development.