Molecular alterations of E-cadherin and beta-catenin in brain metastases

Front Biosci (Elite Ed). 2011 Jan 1;3:616-24. doi: 10.2741/e274.

Abstract

The molecular mechanisms and candidate genes involved in metastasis to the brain need elucidation. In the present study brain metastases were analyzed regarding changes of E-cadherin (CDH1) and beta-catenin (CTNNB1). Loss of heterozygosity (LOH) of the CDH1 gene was detected in 42.2% of samples. The highest frequency of LOHs was observed in metastases from primary sites of lung adenocarcinoma and small cell lung cancer. Metastases from breast and colon demonstrated changes in 55.6% and 50% of cases. Downregulation of E-cadherin protein was observed in 83% of samples. Only 21.1% of samples with E-cadherin LOH had beta-catenin located in the nucleus. Image analysis showed that the quantities of E-cadherin and beta-catenin were significantly positively correlated (P = 0.008). Changes of E-cadherin were frequent in brain metastases that we investigated. Lack of mutations of beta-catenin, the fact that it was not frequently found in the nucleus and the positive correlation between the two proteins may suggest that the break-up of adherens junctions, and not the activation of wnt signaling, is responsible for metastasis formation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adherens Junctions / genetics
  • Adherens Junctions / metabolism*
  • Antigens, CD
  • Brain Neoplasms / genetics
  • Brain Neoplasms / secondary*
  • Cadherins / genetics*
  • Cadherins / metabolism
  • Gene Expression Regulation, Neoplastic / genetics*
  • Humans
  • Image Processing, Computer-Assisted
  • Immunohistochemistry
  • Loss of Heterozygosity / genetics
  • Neoplasm Metastasis / genetics*
  • Neoplasm Metastasis / physiopathology
  • Polymerase Chain Reaction
  • Statistics, Nonparametric
  • beta Catenin / genetics*
  • beta Catenin / metabolism

Substances

  • Antigens, CD
  • CDH1 protein, human
  • CTNNB1 protein, human
  • Cadherins
  • beta Catenin