J Korean Surg Soc.
2008 Dec;75(6):359-367.
Expression of Proteins Related Cell Cycle and Apoptosis during Diethylnitrosamine (DEN)-induced Hepatocarcinogenesis in Rats
- Affiliations
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- 1Department of Surgery, College of Medicine, Chung-Ang University, Seoul, Korea. simon411@hanafos.com
- 2Department of Surgery Pathology, College of Medicine, Chung-Ang University, Seoul, Korea.
Abstract
- PURPOSE
To explore the role of cell cycle and apoptosis regulators during hepatocarcinogenesis, the expression of cell cycle-related proteins (cyclin D1 and p27kip1) and apoptosis-related proteins (p53, survivin, caspase 3).
METHODS
Sprague-Dawley rats were given 120 ppm diethylnitrosamine (DEN) as a carcinogen and sequentially sacrificed. The expression of cell cycle and apoptotic related proteins were examined by light microscopy and immunohistochemistry.
RESULTS
During the DEN-induced hepatocarcinogenesis, sequential histologic changes from preneoplastic lesions (altered hepatic cellular foci, hyperplastic nodules, and hepatocellular adenomas) and ultimately overt hepatocellular carcinomas and metastatic lesions were noted. The cyclin D1 were progressively increased from preneoplastic lesions to hepatocellular carcinomas. However, the p27kip1 and the survivine proteins did not show any other difference with the increasing degree of carcinogenesis. The p53 and caspase 3 proteins were more significantly increased in hepatocellular carcinomas than preneoplastic lesions. The cyclin D1 protein expression did not show any correlation with the expression of p27Kip1 protein, but the p53 expression was related to the expression of survivin and caspase 3.
CONCLUSION
From the above results, over-expression of cyclin D1 plays a role in the early and late stages of hepatocarcinogenesis. In addition p53 and caspase 3 might be useful markers for evaluating the risk of malignant transformation.
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