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- Expression of Glutathione S-Transferase, E-Cadherin, and Catenins during N,N-Diethylnitrosamine-Induced Hepatocarcinogenesis in Rat Liver.
- Hyoung Joong Kim, Yon Sik Yoo, Tae Jin Lee, Mi Kyung Kim, Eon Sub Park, Jae Hyung Yoo
- Korean J Pathol. 2000;34(12):982-993.
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Abstract
PDF - N,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, alpha-catenin, and beta-catenin), which have not been well understood in carcinogenesis, we investigated the changes of E-cadherin, alpha-Catenin and beta-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 alpha- and beta-catenin expression was increased in hyperplastic nodules and hepatocellular carcinomas. Immunoblotting studies revealed that the level of alpha-catenin (cytosol and membranous fraction) was overexpressed in hyperplastic nodules as well as hepatocellular carcinomas, which showed markedly increased expression. The membranous fraction of beta-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 hepato carcinogenesis.
- Promoting Effect of Aflatoxin B1 and D-Galactosamine on Development of Glutathione S-Transferase Positive Foci in Diethylnitrosamine-initiated Rat Liver.
- Hye Kyung Lee, Yong Il Kim
- Korean J Pathol. 1994;28(4):389-398.
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Abstract
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- The enhancing potential of anatoxin a (AFB1) and D-galactosamine (DGA) on development of preneoplastic glutathione S-transferase placental form positive (GST-P+) hepatic foci was examined using an in vivo mid-term assay system based on two-stage concept of hepatocarci-nogenesis. Rats were initially given a single dose (200 mg/kg) of diethylnitrosamine (DEN) intraperi-toneally, and thereafter. with an interval of 2 weeks, AFBl at a graded concentration (0.06, 0.012, 0.0024, 0.00048, and 0.000096 mg/kg i.g.) and DGA (100 mg/kg i.p.) were administered for 6 weeks and then sacrificed. All rats were subjected to a two-thirds partial hepatectomy to induce a potent growth stimulus to DEN-altered hepatocytes at the week 3. The modifying potential was scored by comparing the number and the area (mm2) per cm2 of GST-P+ foci in the liver with those of the corresponding control group given DEN alone. AFBl (at a graded concentration between 96 ng/kg and 60 microgram/kg) exerted a strong promoting effect oil induction of GST-P+ foci with both the number and the area. The logarithmic dose of AFBl and the potency to promote hepatocarcinogenesis were in dose-dependent relationship. DGA, a known necrogenic chemical to cause periportal necrosis and stimulate hepatocellular proliferation. also revealed the increase in the area of GST-P+ foci. although its enhancing potentia1 was 1ess profound than that of AFBl. The results suggest that DGA is also a useful proliferative stimulus m improve the medium-termdetection of unknown carcinogens.
- Immunohistochemical Observation of Placental Form of Glutathione S-Transferase in Squamous Cell Carcinoma.
- Mi Kyung Kim, Jin Seok Seo, Kye Yong Song, Ja June Jang, Sang Chul Park
- Korean J Pathol. 1990;24(3):190-196.
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Abstract
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- Glutathione S-Transferase (GST) is a conjugation enzyme in the metabolism of exogenous and endogenous lipophilic compounds for their excretion and detoxification. Acidic isozyme of GST, GST-Pi, has been recognized as a preneoplastic marker in the experimental hyperplastic nodules of liver in rats, and GST-Pi is abundant in the squamous cells of the skin, also. This histochemical study was carried out to evaluate the distribution and the relationship between the differentiation status of squamous cells in dysplastic or neoplastic epithelium in various organs. The human placental form of glutathione S-transferase (GST-Pi) were stained immunohistochemically with specific anti GST-Pi rabbit antibody in 23 cases of human squamous cell carcinomas. The patients consisted of 14 cases from the uterine cervix, 3 cases from the esopahgus, 3 cases from the lung and 3 cases from the larynx. The results obtained were as follows; 1. Basal cells in normal mucosa were stained negative for GST-Pi while superficial keratinocytes were stained moderately positive. Basal dysplastic cells were stained negatively or weakly positive. Carcinoma cells especially large cells either keratinizing or nonkeratinizing were stained moderately to strongly. Carcinoma cells surrounding keratin pearl were strongly reacted with GST-Pi than other carcinoma cells. 2. Differentiated cells of squamous cell carcinoma showed moderate to strong positive reaction to GST-Pi staining irrespective of its site of origin. 3. Therefore, Immunohistochemical staining pattern of GST-Pi in various squamous carcinoma cells showed similar immunohistochemical reaction to the GST-pi, which is closely correlated to the degree of differentiation, keratinigation and also suggested that squamous carcinoma cells had abundant GST-Pi related detoxifying system.
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