Results of RT-PCR showed the beta-catenin gene exon 3 mRNA Expression Index (EI) of 34 HCCs was higher than that of para-cancerous tissue and normal liver tissue.
Results of RT-PCR showed the beta-catenin gene exon 3 mRNA Expression Index (EI) of 34 HCCs was higher than that of para-cancerous tissue and normal liver tissue.
Our present data suggest that beta-catenin plays important roles in promoting tumor progression by stimulating tumor cell proliferation and reducing the activity of cell adhesion systems and is associated with a poor prognosis, especially in patients with poorly differentiated HCCs.
These results indicate that, in NSCLCs, increased expression of beta-catenin can predict favorable prognosis of patients with resected tumors, suggesting that accumulation of beta-catenin has no or little oncogenic effect via activation of the Wnt pathway, unlike in colon carcinomas or hepatomas.
At difference with a number of epithelial cancers, vascular invasion was frequently noted in HCCs showing enforced expression of the membranous E-cadherin/beta-catenin complex.
Recently, disregulation of the Wnt/beta-catenin pathway, attributable to abnormalities of the beta-catenin gene, has been reported to be a major event in the development of hepatocellular carcinomas and hepatoblastomas.
Here, we provide experimental evidence that wild-type beta-catenin accumulates in hepatocellular carcinoma (HCC) cells in association with mutational inactivation of p53 gene.
In conclusion, although much is still unknown, Gpr49 may be critically involved in the development of HCCs with beta-catenin mutations and has the potential to be a new therapeutic target in the treatment of HCC.
On analyzing the relationship between alterations of beta-catenin or Tcf-4 and C-myc or Cyclin D1 expression, we found that mutations of beta-catenin, as well as overexpression of beta-catenin or the Tcf-4 gene were independently correlated with C-myc gene overexpression in HCC.
In conclusion, LOH and P53 protein overexpression, rather than mutations in the p53 or beta-catenin genes or MSI, seem to be involved in the spreading of HCC, suggesting the presence of metastasis suppressor genes in the vicinity of the chromosomal loci in question.
These results indicate that the altered expression of beta-catenin in HCC may play an important role in tumor progression by stimulating tumor cell proliferation, and nonnuclear overexpression may have pathologic significance in HCC.
Wnt signaling mediated by beta-catenin plays crucial roles in the development of hepatocellular carcinoma and other cancers such as colorectal cancer. beta-Catenin associates with T-cell factor (TCF) transcription factors and functions as a transcriptional activator in the nucleus.
There was, however, a close correlation between nuclear CRBP-1 inclusions and nuclear beta-catenin staining in HCCs (P =.008), suggesting a cross talk between CRBP-1 and the Wnt/wingless signal transduction pathway.
In addition, this is the first report from Malaysia which shows that there are no mutations at the GSK-3beta consensus phosphorylation sites on beta-catenin gene in all 23 paired HCC and surrounding tissues.
In addition, this is the first report from Malaysia which shows that there are no mutations at the GSK-3beta consensus phosphorylation sites on beta-catenin gene in all 23 paired HCC and surrounding tissues.
Sequence analysis of the beta-catenin gene revealed no detectable mutations in DNs, but mutations in the GSK-3beta binding site were present in 14.3% of the HCCs.
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.
However, simultaneous induction of an additional mutation in the beta-catenin gene causes a clonal expansion of such dysplastic cells, followed by nodular formation and development of hepatocellular carcinoma.
The beta-catenin mutations are identified in up to 30% of HCC and 80% of hepatoblastoma, suggesting a potential role of beta-catenin in the pathogenesis of liver cancers.
These results showed that PIN1 overexpression leading to beta-catenin accumulation might be a critical event in hepatocarcinogenesis, and that PIN1 is a potential target for therapeutic intervention in HCC.
A total of 89 HCC samples were analyzed in this study to determine how alterations in the Wnt signaling pathway associate with the carcinogenesis of HCC. beta-catenin immunohistochemistry showed positive nuclear staining in 24 (27.0%) of the 89 HCC samples, indicating the existence of alterations in the Wnt signaling pathway in those 24 HCC samples.
We investigated its function during apoptosis induced by MG132 in three hepatocellular carcinoma (HCC) cell lines, endowed (HepG2 and HuH-6) or not (HA22T/VGH) with activating mutations of beta-catenin.