An Unusual Gene Dosage Effect of p27^kip1 in a Mouse Model of Prostate Cancer

Abstract

Expression of the p27^kip1 cell cycle inhibitor is down-regulated in a wide range of carcinomas, yet it is rarely inactivated completely. Our recent studies of a mouse model of prostate carcinogenesis have revealed that cancer progression is enhanced by a two-fold reduction in p27^kip1 gene dosage, but is unexpectedly inhibited by further decrease in p27^kip1 activity. This paradoxical finding may explain the unusual features of p27^kip1 downregulation in human cancer, and also suggests a potential route for therapeutic intervention.