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.


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


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.
Yoo
N J
NJ
Department of Pathology, College of Medicine, Catholic University of Korea, 505 Banpo-dong, Socho-gu, 137-701 Seoul, Republic of Korea.
Lee
J W
JW
Jeong
E G
EG
Soung
Y H
YH
Nam
S W
SW
Lee
J Y
JY
Lee
S H
SH
D051023:BH3 Interacting Domain Death Agonist Protein / Q000235:genetics*; D006528:Carcinoma, Hepatocellular / Q000235:genetics*; D004252:DNA Mutational Analysis; D022781:Hepatocytes / Q000378:metabolism; D006801:Humans; D007150:Immunohistochemistry; D008113:Liver Neoplasms / Q000235:genetics*; D009154:Mutation; D010766:Phosphorylation; D018807:Polymorphism, Single-Stranded Conformational; D051025:bcl-Associated Death Protein / Q000235:genetics*
C494819:BAD protein, human; D051023:BH3 Interacting Domain Death Agonist Protein; D051025:bcl-Associated Death Protein