Abnormal expression of hepatoma-derived gamma-glutamyltransferase subtyping and its early alteration for carcinogenesis of hepatocytes.
BACKGROUND
Although the hepatoma-specific band of gamma-glutamyltransferase (GGT) is a highly sensitive marker in diagnosis of hepatocellular carcinoma, the kinetic expression and the early alterations of GGT in the development of hepatoma remain unclear. In this study, we investigated the expression and the alterations of GGT multiple molecular forms in hepatotumorigenesis.


METHODS
The expression of GGT in a chemically induced hepatocarcinogenesis model was examined by giving 0.05% of 2-fluoenylacetamide in diet for 12 weeks. The expression levels of total RNA and GGT, and the changes of liver pathology, GGT multiple molecular forms and sugar-chain heterogeneity were investigated at the different stages of rat hepatoma development.


RESULTS
Pathological examination and biochemical analysis found that liver GGT was over-expressed and secreted into blood during canceration. Serum total GGT and liver GGT specific activities (IU/g) including soluble and membrane-combined GGT were significantly higher (P<0.05) in experimental groups than those in control group, respectively. A highly positive correlation was found between total GGT activities and total RNA levels (r=0.90, P<0.05) of the liver. Both were higher six weeks later than before. Con A-non-reactive-GGT was increased consistantly during the development of rat hepatoma. GGT multiple molecular forms in the liver and sera of experimental rats showed that fetal liver-type GGT bands were associated with the development of hepatoma.


CONCLUSIONS
Fetal liver-type GGT in sera and the liver of rats is closely related to hepatotumorigenesis. It can be used as a sensitive enzymatic marker for the early diagnosis of liver cancer.
Yao
Deng-Fu
DF
Research Center of Clinical Molecular Biology, Affiliated Hospital of Nantong University, Nantong 226001, China. dfyrcmb@yahoo.com
Dong
Zhi-Zhen
ZZ
Yao
Deng-Bing
DB
Wu
Xin-Hua
XH
Wu
Wei
W
Qiu
Li-Wei
LW
Wang
Hong-Mei
HM
Meng
Xian-Yong
XY
D000818:Animals; D006528:Carcinoma, Hepatocellular / Q000201:enzymology* / Q000378:metabolism / Q000473:pathology; D004586:Electrophoresis; D022781:Hepatocytes / Q000201:enzymology*; D007527:Isoenzymes / Q000378:metabolism*; D008099:Liver / Q000378:metabolism; D008114:Liver Neoplasms, Experimental / Q000201:enzymology* / Q000378:metabolism / Q000473:pathology; D008297:Male; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D005723:gamma-Glutamyltransferase / Q000097:blood / Q000378:metabolism*
D007527:Isoenzymes; D012333:RNA, Messenger; D005723:gamma-Glutamyltransferase