We detected seven somatic mutations in a portion of exon 3 encoding for the glycogen synthase kinase 3beta phosphorylation consensus region of the beta-catenin gene in 43 gastric cancers.
These results strongly suggest that WNT3 might play a key role in some cases of human breast, rectal, lung, and gastric cancer through activation of the WNT - beta-catenin - TCF signaling pathway, similar to mouse Wnt-3.
In addition, the immunohistochemical expression pattern of beta-catenin in 303 consecutive gastric cancers was determined and their relationships with clinicopathologic features and patient outcome were investigated.
Our findings suggest that somatic mutations of the beta-catenin gene are rare in human gastric carcinomas and that accumulation of normal beta-catenin protein in a subset of gastric cancers may be due to other mechanisms of its activation.
These results strongly suggest that up-regulation of WNT10A induced by TNFalpha and H. pylori might play key roles in human gastric cancer through activation of WNT--beta-catenin--TCF signaling pathway.
A beta-catenin gene mutation was identified only in one intestinal-type gastric cancer exhibiting a massive overexpression of beta-catenin mRNA in the tumour.
Examples of genes involved in pathogenesis of GC include p53, adenomatous polyposis coli (APC), beta-catenin, E-cadherin, transforming growth factor (TGF)-betaRII, and hMLH1.
Immunohistochemistry and Western blot analysis were used to analyze the expression of beta-catenin in 87 human gastric cancers, in metastasis and cancer cell lines.
Adenomatous polyposis coli gene, beta-catenin, and E-cadherin expression in proximal and distal gastric cancers and precursor lesions: an immunohistochemical study using tissue microarrays.
These biological factors are often derived from the genetic process, which is thought to represent a crucial step to gastric cancer (DNA copy number changes, microsatellite instability, thymidilate synthase, E-cadherin, beta-catenin, mucin antigen, p53, c-erb B-2, COX-2, matrix metalloproteinases, VEGFR and EGFR).
These data suggest that inactivating mutations of the Siah-1 may contribute to the development of gastric cancer through beta-catenin stabilization and apoptosis block.
The loss of membranous and the gain of cytoplasmic and nuclear beta-catenin in gastric cancers checked in this study are not due to the mutational event. beta-catenin molecules translocalized in the nuclei are closely correlated with tumor invasion.
By the methods of frozen tissue array-based immunohistochemistry, Western blot analysis and RT-PCR, a paralleled study was conducted to check Wnt2 expression and beta-catenin intracellular distribution in two major subtypes of gastric cancers (intestinal gastric cancer, i-GC and diffuse gastric cancer, d-GC) and their premalignant (intestinal metaplasia, IM and chronic gastritis, CG) and noncancerous counterparts.
So far, the combined status of beta-catenin and TCF4 and its relevance for lymph node metastasis and CD44 expression have not been well studied in gastric cancers (GCs).
In this study, we investigated whether gene amplification is a possible mechanism of beta-catenin activation in gastric cancer by determining its presence in 49 patients with gastric cancer and two gastric-derived cell lines (KATO III and ST2957).
Beta-catenin gene (CTNNB1) mutations have been described predominantly in intestinal-type gastric cancers and CTNNB1 gene amplification and overexpression have recently been described in a mixed-type gastric cancer.