Expressional analysis of anti-apoptotic phospho-BAD protein and mutational analysis of pro-apoptotic BAD gene in hepatocellular carcinomas

Dig Liver Dis. 2006 Sep;38(9):683-7. doi: 10.1016/j.dld.2006.05.018. Epub 2006 Jun 27.

Abstract

Background: It has become clear that, together with proliferation, deregulation of apoptosis plays a pivotal role in tumourigenesis. BAD is a pro-apoptotic Bcl-2 family protein and regulates the intrinsic apoptosis pathway. Phosphorylation of BAD inhibits the apoptosis function of BAD.

Aims: To investigate whether alteration of the phospho-BAD protein and somatic mutation of BAD gene are characteristics of human hepatocellular carcinoma.

Patients and methods: We analysed the expression of phospho-BAD in 20 hepatocellular carcinomas by immunohistochemistry. Also, we analysed the BAD gene for the detection of somatic mutations by a single-strand conformation polymorphism assay in 69 hepatocellular carcinomas.

Results: Phospho-BAD expression in the non-tumour hepatocytes was seen in all of the hepatocellular carcinomas, while the expression in the cancer cells was observed in 15% (3 of the 20) of the hepatocellular carcinomas. There was no somatic mutation of BAD Bcl-2 homology 3 (BH3) domain in the 69 hepatocellular carcinomas.

Conclusions: The data showed that loss of phospho-BAD expression, but not BAD gene mutation, is a feature of hepatocellular carcinomas. The decreased expression of phospho-BAD in the hepatocellular carcinoma cells compared to the non-tumour hepatocytes suggests that loss of phospho-BAD expression may play a role in hepatocellular tumourigenesis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • BH3 Interacting Domain Death Agonist Protein / genetics*
  • Carcinoma, Hepatocellular / genetics*
  • DNA Mutational Analysis
  • Hepatocytes / metabolism
  • Humans
  • Immunohistochemistry
  • Liver Neoplasms / genetics*
  • Mutation*
  • Phosphorylation
  • Polymorphism, Single-Stranded Conformational
  • bcl-Associated Death Protein / genetics*

Substances

  • BAD protein, human
  • BH3 Interacting Domain Death Agonist Protein
  • bcl-Associated Death Protein