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
in English
| WPRIM
| ID: wpr-235857
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>
Full text:
Available
Index:
WPRIM (Western Pacific)
Main subject:
Physiology
/
Transcription Factors
/
Immunohistochemistry
/
Trans-Activators
/
Polymerase Chain Reaction
/
Proto-Oncogene Proteins
/
Carcinoma, Hepatocellular
/
Polymorphism, Single-Stranded Conformational
/
Reverse Transcriptase Polymerase Chain Reaction
/
Cytoskeletal Proteins
Limits:
Humans
Language:
English
Journal:
Chinese Medical Journal
Year:
2003
Type:
Article
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