Alterations of beta-catenin and Tcf-4 instead of GSK-3beta contribute to activation of Wnt pathway in hepatocellular carcinoma / 中华医学杂志(英文版)
Chinese Medical Journal
; (24): 1885-1892, 2003.
Article
em En
| WPRIM
| ID: wpr-235857
Biblioteca responsável:
WPRO
ABSTRACT
<p><b>OBJECTIVE</b>The goal of this study is to investigate the inappropriate activation of Wnt pathway in the hepatocarcinogenesis.</p><p><b>METHODS</b>We analyzed the alterations of three key components of Wnt pathway, beta-catenin, glycogen synthase kinase 3beta (GSK-3beta) and T cell factor 4 (Tcf-4), in 34 samples of hepatocellular carcinoma (HCC) and paracancerous normal liver by immunohistochemistry, polymerase chain reaction-single strand conformation polymorphism (PCR-SSCP), direct sequencing, semi-quantitative reverse transcription-polymerase chain reaction (RT-PCR) and in situ hybridization.</p><p><b>RESULTS</b>We found 61.8% (21/34) of all the HCCs examined showed an abnormal beta-catenin protein accumulation in the cytoplasm or nuclei. RT-PCR-SSCP and direct sequencing showed that beta-catenin exon 3 mutations existed in 44.1% (15/34) of the HCCs. No mutations of GSK-3beta or Tcf-4 were detected in HCCs. Moreover, mRNA of beta-catenin and Tcf-4 but not GSK-3beta was found to be over expressed in HCCs. On analyzing the relationship between alterations of beta-catenin or Tcf-4 and C-myc or Cyclin D1 expression, we found that the mutations of beta-catenin as well as over expression of beta-catenin or Tcf-4 gene were independently correlated with C-myc gene over expression in HCCs.</p><p><b>CONCLUSIONS</b>Our present findings strongly suggest mutations of beta-catenin as well as over expression of beta-catenin and Tcf-4 gene activate the Wnt pathway in HCC independently with the target gene most likely to be C-myc.</p>
Texto completo:
1
Índice:
WPRIM
Assunto principal:
Fisiologia
/
Fatores de Transcrição
/
Imuno-Histoquímica
/
Transativadores
/
Reação em Cadeia da Polimerase
/
Proteínas Proto-Oncogênicas
/
Carcinoma Hepatocelular
/
Polimorfismo Conformacional de Fita Simples
/
Reação em Cadeia da Polimerase Via Transcriptase Reversa
/
Proteínas do Citoesqueleto
Limite:
Humans
Idioma:
En
Revista:
Chinese Medical Journal
Ano de publicação:
2003
Tipo de documento:
Article