Correlation of Wnt-2 expression and beta-catenin intracellular accumulation in Chinese gastric cancers: relevance with tumour dissemination

Cancer Lett. 2005 Jun 8;223(2):339-47. doi: 10.1016/j.canlet.2004.11.013. Epub 2004 Dec 13.

Abstract

Wnt/beta-catenin signalling pathway is integrally associated with human tumour development and progression. Aberrant beta-catenin intracellular distribution has been found in gastric cancer, but the pattern of Wnt expression in stepwise gastrocarcinogenesis and its potential influence in beta-catenin distribution are still lesser known. 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. According to the results obtained and the clinical data collected, correlation of Wnt2 expression with beta-catenin translocalisation and their links with tumour dissemination were elucidated. The results demonstrated (1) that Wnt2 expression and cytoplasmic/nuclear beta-catenin accumulations appeared in most gastric cancers irrespective to their morphological phenotypes, (2) that over-expressed Wnt and nuclear translocalisation of beta-catenin were found in 68 and 58% of i-GCs and in 47 and 47% of d-GCs in a closely related pattern (P<0.01) and (3) that co-existence of Wnt2 up-regulation/beta-catenin nuclear translocalisation were positively associated with lymph node metastasis (P<0.05) as well as T-stage. These data indicate that Wnt/beta-catenin signalling pathway is activated in most of gastric cancers, which may play pivotal roles either in gastric cancer formation or in tumour invasion and dissemination.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Blotting, Western
  • Cell Nucleus / chemistry
  • Cell Transformation, Neoplastic
  • China
  • Cytoplasm
  • Cytoskeletal Proteins / biosynthesis*
  • Cytoskeletal Proteins / pharmacokinetics*
  • Gene Expression Profiling*
  • Humans
  • Immunohistochemistry
  • Neoplasm Invasiveness
  • Neoplasm Metastasis
  • Precancerous Conditions
  • Proto-Oncogene Proteins / biosynthesis*
  • Proto-Oncogene Proteins / pharmacokinetics*
  • Reverse Transcriptase Polymerase Chain Reaction
  • Signal Transduction
  • Stomach Neoplasms / genetics*
  • Stomach Neoplasms / physiopathology*
  • Trans-Activators / biosynthesis*
  • Trans-Activators / pharmacokinetics*
  • Up-Regulation
  • Wnt2 Protein
  • beta Catenin

Substances

  • CTNNB1 protein, human
  • Cytoskeletal Proteins
  • Proto-Oncogene Proteins
  • Trans-Activators
  • Wnt2 Protein
  • beta Catenin