An unusual gene dosage effect of p27kip1 in a mouse model of prostate cancer.
Expression of the p27kip1 cell cycle inhibitor is downregulated 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 p27kip1 gene dosage, but is unexpectedly inhibited by further decrease in p27kip1 activity. This paradoxical finding may explain the unusual features of p27kip1 downregulation in human cancer, and also suggests a potential route for therapeutic intervention.
Abate-Shen
Cory
C
Center for Advanced Biotechnology and Medicine, Department of Medicine, Cancer Institute of New Jersey, UMDNJ-Robert Wood Johnson Medical School, 679 Hoes Lane, Piscataway, NJ 08854, USA. abate@cabm.rutgers.edu
Shen
Michael M
MM
D000818:Animals; D002453:Cell Cycle; D019938:Cyclin D1 / Q000378:metabolism; D050760:Cyclin-Dependent Kinase Inhibitor p27 / Q000235:genetics*; D004195:Disease Models, Animal; D018450:Disease Progression; D015536:Down-Regulation; D018628:Gene Dosage; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D009154:Mutation; D010641:Phenotype; D011471:Prostatic Neoplasms / Q000235:genetics*
D019938:Cyclin D1; D050760:Cyclin-Dependent Kinase Inhibitor p27