Expression of β-catenin protein in hepatocellular carcinoma and its relationship with alpha-fetoprotein

J Huazhong Univ Sci Technolog Med Sci. 2016 Dec;36(6):846-851. doi: 10.1007/s11596-016-1673-9. Epub 2016 Dec 7.

Abstract

This study aimed to investigate the expression of β-catenin in hepatocellular carcinoma (HCC) tissues and its relationship with α-fetoprotein (AFP) in HCC. Immunohistochemistry was used to determine the expression of β-catenin in normal liver tissues (n=10), liver cirrhosis tissues (n=20), and primary HCC tissues (n=60). The relationship between β-catenin expression and clinical parameters of HCC was investigated. Real-time PCR and Western blotting were used to detect the mRNA and protein expression levels of β-catenin in the liver cancer cell line SMMC-7721 transfected with a plasmid encoding AFP, and also the mRNA and protein expression levels of β-catenin were measured in the liver cancer cell line Huh7 before and after the transfection with AFP shRNA plasmids. The results showed that β-catenin was only expressed on the cell membrane in normal liver tissues. Its localization to the cytoplasm and nucleus of cells was observed in a small proportion of cirrhotic tissues or adjacent HCC tissues, and such ectopic expression of β-catenin was predominant in HCC tissues. The abnormal expression of β-catenin was correlated with serum AFP levels, cancer cell differentiation and vascular invasion (P<0.05). Additionally, the increased expression of AFP resulted in the upregulation of β-catenin mRNA and protein levels, while knockdown of AFP with AFP shRNA led to significantly decreased β-catenin mRNA and protein levels (P<0.05). It was suggested that the abnormal expression of β-catenin is implicated in hepatic carcinogenesis and development. AFP can lead to increased expression of β-catenin, which may account for the poor prognosis of AFP-associated HCC patients.

Keywords: hepatocellular carcinoma; α-fetoprotein; β-catenin.

MeSH terms

  • Active Transport, Cell Nucleus
  • Adult
  • Aged
  • Biomarkers, Tumor / genetics
  • Biomarkers, Tumor / metabolism*
  • Carcinoma, Hepatocellular / genetics
  • Carcinoma, Hepatocellular / metabolism*
  • Carcinoma, Hepatocellular / pathology
  • Cell Line, Tumor
  • Cell Nucleus / metabolism
  • Female
  • Humans
  • Liver / metabolism
  • Liver Cirrhosis / genetics
  • Liver Cirrhosis / metabolism
  • Liver Cirrhosis / pathology
  • Liver Neoplasms / genetics
  • Liver Neoplasms / metabolism*
  • Liver Neoplasms / pathology
  • Male
  • Middle Aged
  • alpha-Fetoproteins / genetics
  • alpha-Fetoproteins / metabolism*
  • beta Catenin / genetics
  • beta Catenin / metabolism*

Substances

  • AFP protein, human
  • Biomarkers, Tumor
  • alpha-Fetoproteins
  • beta Catenin