Yoo N J, Lee J W, Jeong E G, Soung Y H, Nam S W, Lee J Y, Lee S H
Department of Pathology, College of Medicine, Catholic University of Korea, 505 Banpo-dong, Socho-gu, 137-701 Seoul, Republic of Korea.
Dig Liver Dis. 2006 Sep;38(9):683-7. doi: 10.1016/j.dld.2006.05.018. Epub 2006 Jun 27.
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.
To investigate whether alteration of the phospho-BAD protein and somatic mutation of BAD gene are characteristics of human hepatocellular carcinoma.
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.
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.
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.
现已明确，除增殖外，凋亡失调在肿瘤发生过程中起关键作用。BAD是一种促凋亡的Bcl-2家族蛋白，可调节内源性凋亡途径。BAD的磷酸化会抑制其凋亡功能。
研究磷酸化BAD蛋白的改变以及BAD基因的体细胞突变是否为人类肝细胞癌的特征。
我们通过免疫组织化学分析了20例肝细胞癌中磷酸化BAD的表达。此外，我们采用单链构象多态性分析方法，对69例肝细胞癌的BAD基因进行了体细胞突变检测。
在所有肝细胞癌中均可见非肿瘤肝细胞中有磷酸化BAD表达，而在15%（20例中的3例）的肝细胞癌的癌细胞中观察到有该表达。69例肝细胞癌中BAD的Bcl-2同源结构域3（BH3）未发生体细胞突变。
数据表明，磷酸化BAD表达缺失而非BAD基因突变是肝细胞癌的一个特征。与非肿瘤肝细胞相比，肝细胞癌细胞中磷酸化BAD表达降低，提示磷酸化BAD表达缺失可能在肝细胞癌发生过程中起作用。
