Insulin-like growth factor binding protein-4 gene silencing in lung adenocarcinomas.
Pathol Int
; 61(1): 19-27, 2011 Jan.
Article
em En
| MEDLINE
| ID: mdl-21166939
ABSTRACT
Gene silencing by promoter hypermethylation plays an important role in molecular pathogenesis. We previously reported that insulin-like growth factor (IGF) binding protein-4 (IGFBP-4), which inhibits IGF-dependent growth, is expressed via early growth response-1 (EGR-1) and is often silenced in cultivated lung cancer cells. The purpose of the present study was to clarify clinicopathological factors associated with IGFBP-4 gene silencing in lung adenocarcinomas. Seventy-six surgically resected adenocarcinomas (20 well-, 35 moderately-, and 21 poorly-differentiated) were subjected to methylation-specific polymerase chain reaction (PCR) analysis for EGR-1-binding sites located in the IGFBP-4 promoter and immunohistochemistry for IGFBP-4, EGR-1, and Ki-67. Thirty-two adenocarcinomas (42%) revealed IGFBP-4 promoter hypermethylation, and the severity inversely correlated with the level of IGFBP-4 expression (P < 0.0001) and tumor differentiation (well versus poor, P = 0.0278; well/moderate versus poor, P = 0.0395). Furthermore, there was a negative correlation between Ki-67 labeling index and IGFBP-4 expression (P = 0.0361). These findings suggest that the expression of IGFBP-4 in adenocarcinoma cells in vivo is downregulated by epigenetic silencing in association with tumor differentiation, resulting in disruption of the mechanism of IGFBP-4-mediated growth inhibition.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Adenocarcinoma
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Proteína 4 de Ligação a Fator de Crescimento Semelhante à Insulina
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Inativação Gênica
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Neoplasias Pulmonares
Limite:
Humans
Idioma:
En
Ano de publicação:
2011
Tipo de documento:
Article