Role of the CDK inhibitor p27 (Kip1) in mammary development and carcinogenesis: insights from knockout mice.
The cyclin-dependent kinase inhibitor p27 (Kip1) is an important cell cycle regulatory gene in breast cancer, and decreased p27 expression is associated with poor prognosis. Some investigations of its role in mammary development have demonstrated reduced cyclin D1 expression and consequent lack of lobuloalveolar development, but others have found increased cyclin E-Cdk2 activity and increased proliferation balanced by increased apoptosis. It is unclear at present why these apparently divergent results have been obtained. Mice with reduced p27 gene dosage alone do not develop mammary carcinomas but do display substantially shorter tumor latency upon overexpression of erbB2, consistent with a role for p27 as a mammary tumor suppressor gene. In this review we summarize these and other data addressing the role of p27 in normal mammary epithelium and experimental models of mammary carcinogenesis.
Musgrove
Elizabeth A
EA
Cancer Research Program, Garvan Institute of Medical Research, St Vincent's Hospital, Sydney, Australia. e.musgrove@garvan.org.au
Davison
Elizabeth A
EA
Ormandy
Christopher J
CJ
D000818:Animals; D017209:Apoptosis; D001943:Breast Neoplasms / Q000235:genetics* / Q000503:physiopathology*; D002277:Carcinoma / Q000235:genetics* / Q000503:physiopathology*; D002453:Cell Cycle; D018797:Cell Cycle Proteins / Q000235:genetics* / Q000494:pharmacology*; D049109:Cell Proliferation; D002471:Cell Transformation, Neoplastic; D050760:Cyclin-Dependent Kinase Inhibitor p27; D004195:Disease Models, Animal; D004791:Enzyme Inhibitors; D005260:Female; D016147:Genes, Tumor Suppressor; D006801:Humans; D008321:Mammary Glands, Animal / Q000473:pathology; D042361:Mammary Glands, Human / Q000254:growth & development* / Q000502:physiology; D015674:Mammary Neoplasms, Animal / Q000235:genetics / Q000503:physiopathology; D051379:Mice; D011379:Prognosis; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000502:physiology; D025521:Tumor Suppressor Proteins / Q000235:genetics* / Q000494:pharmacology*
D018797:Cell Cycle Proteins; D050760:Cyclin-Dependent Kinase Inhibitor p27; D004791:Enzyme Inhibitors; D018719:Erb-b2 Receptor Tyrosine Kinases; D025521:Tumor Suppressor Proteins; C493961:Cdkn1b protein, mouse