N,N-Diethylnitrosamine에 의한 흰쥐 간암종발생과정에서 Glutathione S-Transferase, E-Cadherin 및 Catenins의 발현
Expression of Glutathione S-Transferase, E-Cadherin, and Catenins during N,N-Diethylnitrosamine-Induced Hepatocarcinogenesis in Rat Liver
김형중, 유연식, 이태진, 김미경, 박언섭, 유재형,
소속 상세정보
김형중 ( Kim Hyoung-Joong )
중앙대학교 의과대학 병리학교실
유연식 ( Yoo Yon-Sik )
중앙대학교 의과대학 병리학교실
이태진 ( Lee Tae-Jin )
중앙대학교 의과대학 병리학교실
김미경 ( Kim Mi-Kyung )
중앙대학교 의과대학 병리학교실
박언섭 ( Park Eon-Sub )
중앙대학교 의과대학 병리학교실
유재형 ( Yoo Jae-Hyung )
중앙대학교 의과대학 병리학교실
KMID : 0357920000340120982
Abstract
NN,N-Diethylnitrosamine (DEN) has been proved to have carcinogenic potential in the initiation or promotion stage and the transformed cells proliferate to form preneoplastic nodules which are positive for placental form of glutathione S-transferase (GST-P). E-Cadherin, a member of the cadherin family, is expressed in epithelial cells. To evaluate the role of adhesion molecules (E-Cadherin, α-catenin, and β-catenin), which have not been well understood in carcinogenesis, we investigated the changes of E-cadherin, α-Catenin and β-Catenins by immunohistochemistry and immunoblotting in DEN-induced hepatocarcinogenesis of rat liver. In addition, the sequential analysis of histopathology and the expression of GST-P were also examined. Immunoreactive areas for GST-P were gradually increased from early period of carcinogenesis and strong GST-P positive foci were noted in various lesions, especially in the clear cell and eosinophilic cell nodules. Immunohistochemically, the E-Cadherin expression was increased in DEN-treated preneoplastic nodules in 4 and 10 weeks and hepatocellular carcinomas displayed relatively reduced expression compared with the hyperplastic nodules. But α- and β-catenin expression was increased in hyperplastic nodules and hepatocellular carcinomas. Immunoblotting studies revealed that the level of α-catenin (cytosol and membranous fraction) was overexpressed in hyperplastic nodules as well as hepatocellular carcinomas, which showed markedly increased expression. The membranous fraction of β-catenin was markedly increased in 10 weeks of DEN treatment and slightly reduced in hepatocellular carcinomas. These findings suggest that during DEN-induced hepatocarcinogenesis, the clear cell and eosinophilic cell nodules expressing GST-P in their cytoplasm are early transformed cell nodules. The altered expression of E-Cadherin and catenins is closely related with tumor propagation. Loss or reduced expression of E-cadherin may play a role in the progression of late hyperplastic nodule to hepatocellular carcinoma in DEN-induced rat hepatocarcinogenesis.
키워드
Rat hepatocarcinogenesis;N;N-Diethylnitrosamine;GST-P;E-Cadherin;Catenins
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