Haploinsufficiency of p18(INK4c) sensitizes mice to carcinogen-induced tumorigenesis.
Mol Cell Biol
; 23(4): 1269-77, 2003 Feb.
Article
em En
| MEDLINE
| ID: mdl-12556487
ABSTRACT
The INK4 family of cyclin-dependent kinase (CDK) inhibitors negatively regulates cyclin D-dependent CDK4 and CDK6 and thereby retains the growth-suppressive function of Rb family proteins. Mutations in the CDK4 gene conferring INK4 resistance are associated with familial and sporadic melanoma in humans and result in a wide spectrum of tumors in mice. Whereas loss of function of other INK4 genes in mice leads to little or no tumor development, targeted deletion of p18(INK4c) causes spontaneous pituitary tumors and lymphoma late in life. Here we show that treatment of p18 null and heterozygous mice with a chemical carcinogen resulted in tumor development at an accelerated rate. The remaining wild-type allele of p18 was neither mutated nor silenced in tumors derived from heterozygotes. Hence, p18 is a haploinsufficient tumor suppressor in mice.
Texto completo:
1
Bases de dados:
MEDLINE
Assunto principal:
Carcinógenos
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Proteínas de Ciclo Celular
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Predisposição Genética para Doença
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Proteínas Supressoras de Tumor
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Neoplasias Experimentais
Limite:
Animals
Idioma:
En
Revista:
Mol Cell Biol
Ano de publicação:
2003
Tipo de documento:
Article
País de afiliação:
Estados Unidos