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

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.