Tgfbr1 haploinsufficiency inhibits the development of murine mutant Kras-induced pancreatic precancer.
Cancer Res
; 69(24): 9169-74, 2009 Dec 15.
Article
em En
| MEDLINE
| ID: mdl-19951995
ABSTRACT
To dissect the role of constitutively altered Tgfbr1 signaling in pancreatic cancer development, we crossed Elastase-Kras(G12D) (EL-Kras) mice with Tgfbr1 haploinsufficient mice to generate EL-Kras/Tgfbr1(+/-) mice. Mice were euthanized at 6 to 9 months to compare the incidence, frequency, and size of precancerous lesions in the pancreas. Only 50% of all EL-Kras/Tgfbr1(+/-) mice developed preinvasive lesions compared with 100% of EL-Kras (wild-type Tgfbr1) mice. The frequency of precancerous lesions was 4-fold lower in haploinsufficient than in control mice. Paradoxically, the precancerous lesions of EL-Kras/Tgfbr1(+/-) mice were considerably larger than those in EL-Kras mice. Yet, the mitotic index of precancerous cells and the observable levels of fibrosis, lipoatrophy, and lymphocytic infiltration were reduced in EL-Kras/Tgfbr1(+/-) mice. We conclude that Tgfbr1 signaling promotes the development of precancerous lesions in mice. These findings suggest that individuals with constitutively decreased TGFBR1 expression may have a decreased risk of pancreatic cancer.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Neoplasias Pancreáticas
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Lesões Pré-Cancerosas
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Proteínas Proto-Oncogênicas p21(ras)
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Proteínas Serina-Treonina Quinases
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Receptores de Fatores de Crescimento Transformadores beta
Limite:
Animals
Idioma:
En
Revista:
Cancer Res
Ano de publicação:
2009
Tipo de documento:
Article
País de afiliação:
Estados Unidos