Exp Mol Med.
1998 Mar;30(1):35-40.
Telomerase is strongly activated in hepatocellular carcinoma but not in chronic
hepatitis and cirrhosis
- Affiliations
-
- 1Department of Internal Medicine, Kangnam St. Mary's Hospital, College of
Medicine, Catholic University, Seoul, Korea
Abstract
- Telomerase is highly activated in human immortal cell lines and tumor tissues,
whereas it is not activated in primary cell strains and many tumor-adjacent
tissues. It is suggested that telomerase activation is one of the critical steps
in malignant transformation. In the present study, the telomerase activity was
investigated in hepatocellular carcinoma tissues and non-tumor liver tissues
from Korean patients with chronic hepatitis and cirrhosis. Eighty two liver
tissues (24 chronic hepatitis specimens, 34 cirrhosis specimens, and 24
hepatocellular carcinomas) were obtained from 23 chronic viral hepatitis
patients, 19 cirrhosis patients (including 7 liver transplants), and 24 patients
with hepatocellular carcinoma, of which the surrounding non-tumor liver tissues
were available in 16 patients (1 chronic hepatitis and 15 cirrhosis). As
negative controls, 3 normal liver tissues were included. Protein from liver
specimens was purified by a detergent lysis method as described elsewhere, and
telomerase activity was measured in 2 diluents of each sample (1:1 and 1:100) by
a telomeric repeat amplification protocol (TRAP). Telomerase was strongly
activated in 79% (19/24) of the hepatocellular carcinomas, while weakly in 8%
(2/24) of the chronic hepatitis tissues and in 24% (8/34) of the cirrhosis
tissues. All of 3 normal control livers showed no telomerase activation. No
relationship could be observed between the enhancement of telomerase activity
and tumor nature. None of the chronic heaptitis or cirrhosis patients with mild
telomerase activation in the liver have developed hepatocellular carcinoma for
at least 2 years of follow-up period. These results suggest that the strong
enhancement of telomerase activity may be a critical part of
hepatocarcinogenesis, although the exact mechanism of such high activation in
hepatocellular carcinoma is not clear. In addition, further study will be
necessary to clarify the reason why no telomerase activity detectable by a
conventional TRAP can be seen in some hepatocellular carcinoma.