p27Kip1 is inactivated in human colorectal cancer by cytoplasmic localization associated with activation of Akt/PKB.
Int J Oncol
; 34(1): 69-77, 2009 Jan.
Article
em En
| MEDLINE
| ID: mdl-19082479
ABSTRACT
p27Kip1 is a nuclear member of the Kip/Cip family of cyclin-dependent kinase inhibitors and is a negative cell cycle regulator that is thought to play a role in tumour suppression. Reduced levels of p27Kip1 are frequent in human cancers and these have been associated with poor prognosis. We have analysed p27Kip1 expression and intracellular localization in 70 human colorectal cancers by western blotting and immunohistochemistry and the results related to Akt expression and clinical pathological parameters. p27Kip1 protein expression, as evaluated by western blotting, was absent or reduced in about 63% of colorectal cancers compared with both peritumoral and normal tissue. Cytoplasmic p27Kip1 was detected, by immunohistochemical analysis, in 30% (21 of 70) of cases indicating that translocation of p27Kip1 protein into the cytoplasm may be responsible for p27Kip1 inactivation. The analysis of phosphorylated Akt by western blotting indicated that it was expressed in 38% (8 of 21) of tumours showing cytoplasmic p27Kip1. Patients whose cancer presented accumulation of cytoplasmic p27Kip1 showed poorer outcomes for cancer-related relapse and survival. These results suggest that cytoplasmic p27Kip1 localization, associated or not with Akt activation, may contribute to colorectal tumorigenesis and metastasis and it may be useful as a negative prognostic factor for the outcome of patients with colorectal cancer.
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Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Neoplasias Colorretais
/
Biomarcadores Tumorais
/
Citoplasma
/
Proteínas Proto-Oncogênicas c-akt
/
Inibidor de Quinase Dependente de Ciclina p27
Tipo de estudo:
Prognostic_studies
/
Risk_factors_studies
Limite:
Adult
/
Aged
/
Aged80
/
Female
/
Humans
/
Male
/
Middle aged
Idioma:
En
Revista:
Int J Oncol
Assunto da revista:
NEOPLASIAS
Ano de publicação:
2009
Tipo de documento:
Article
País de afiliação:
Itália