백서 N-nitrosomorpholine Stop Experiment시 발생하는간세포 종양과 전구병변에서의 PDGF-Rα 발현
PDGF-Rα Expression in Preneoplastic and Neoplastic Hepatocellular Lesions: A Rat Model N-nitrosomorpholineStop Experiment
0
조회
0
다운로드
0
인용
0
참고문헌
초록
Abstract
Background : N-nitrosomorpholine (NNM) is a genotoxic hepatocarcinogenic agent. Preneoplastic and neoplastic hepatocyte lesions were induced in rats by oral exposure to NNM (200 mg/L) in a stop model experiment. Platelet-derived growth factor receptor (PDGF-R) is a tyrosine kinase receptor that works with PDGF, stimulating cellular growth and proliferation. The present study was designed to determine the role of PDGF-Rα expression in hepatocellular neoplasms and precursors. Methods : Seventeen rats out of a starting number of 30 died. From the fifth week until the 24th week one or two rats were evaluated. Preneoplastic single cells or foci, foci of altered hepatocytes (FAH) hepatocellular adenomas (HCA) and hepatocellular carcinomas (HCC) were studied histologically, and the expressions of GSTp and PDGF-Rα by immunohistochemistry. Results : At the fifth week, GSTp+ single cells showed PDGF-Rα expression (20.8±5.8%). At the sixth week, GSTp+ single cells, located at periportal areas, co-expressed PDGF-Rα (43.4±9.6%). Over the next several weeks periportal hepatocytes showed weaker PDGF-Rα expression but no GSTp. GSTp+ FAH, and all HCA, demonstrated no PDGF-Rα expression. However, nine out of 10 (90%) HCC showed PDGF-Rα expression. Conclusions : These data showed that there were two peaks of PDGF-Rα expression, and suggest that the earlier expression is related with the response to NNM-induced hepatocyte toxicity, and that the later response is associated to malignant transformation.
참고문헌 (26)
- "The rat liver hepatocellular-altered focus-limited bioassay for chemicals with carcinogenic activity carcinogenecity", pp.361~394 (1999), Marcel Dekker, Inc.
- "and cancer of the lung and pancreas in humans origins of human cancer", -1-buta(ne), pp.4 3 145~55 (1991), Cold Spring Harbor Laboratory Press
- "Preneoplastic lesions as end points in carcinogenicity testing I", 7, pp.689~95 (1986)
- "Preneoplastic lesions as end points in carcinogenicity testing II", 7, pp.849~52 (1986)
- "Pathology of Tumors in Laboratory Animals Tumors of the Rat Tumors of the liver"
- "Pathogenesis of hepatocellular carcinoma:sequential cellular,molecular and metabolic changes", 14, pp.161~197 (1996)
- "Platelet-derived growth factor receptors:a therapeutic target in solid tumors", 28, pp.27~33 (2001)
- "Targeting PDGF receptors in cancer--rationales and proof of concept clinical trials", 532, pp.141~151 (2003)
- "Platelet-derived growth factor receptor-mediated signal transduction from endosomes", 279, pp.8038~8046 (2004)
- "Role of myofibroblasts in tumour encapsulation of hepatocellular carcinoma in hemochromatosis", 21, pp.96~104 (2001)
- "Green tea polyphenol epigallocatechin-3-gallate inhibits plateletderived growth factor-induced proliferation of human hepatic stellate cell line LI90", 40, pp.52~59 (2004)
- "The role of platelet-derived growth factor and ras P21 in experimental hepatocarcinogenesis", 25, pp.79~82 (1996)
- "Single GSTP positive liver cells--putative initiated hepatocytes", 8, pp.483~6 (1987)
- "Comparison of hepatocyte phenotypes at the glutathione transferase and albumin loci in Sprague-Dawley and Nagase analbuminemic rats and F1 progeny after initiation and promotion", 14, pp.1313~9 (1993)
- "The dose dependence and sequential appearance of putative preneoplastic populations induced in the rat liver by stop experiments with N-nitrosomorpholine", 3, pp.1429~36 (1982)
- "Light microscopic studies on the effects of N-nitrosomorpholine on the liver of rats and mice", 14, pp.805~14 (1964)
- "Inhibition of apoptosis during 2, 3, 7, 8-tetrachlorodibenzo-p-dioxin-mediated tumour promotion in rat liver", 16, pp.1271~1275 (1995)
- "Quantitative analysis of tumor initiation in rat liver:role of cell replication and cell death(apoptosis)", 21, pp.1411~1421 (2000)
- "Glutathione transferase as markers for preneoplasia and neoplasia The biology of cancer Advanced in cancer Research Academic Press", pp.205~8 (1989)
- "DNA synthesis,apoptosis,and phenotypic expression as determinants of growth of altered foci in rat liver during phenobarbital promotion", 50, pp.5127~35 (1990)
- "Signal transduction in hepatic stellate cells", 18, pp.2~13 (1998)
- "Phosphatidylinositol 3-kinase is required for platelet-derived growth factor's actions on hepatic stellate cells", 112, pp.1297~1306 (1997)
- "Parallel hybridization analysis of multiple protein kinase genes:identification of gene expression patterns characteristic of human hepatocellular carcinoma", 50, pp.331~340 (1998)
- "Myxoid epithelioid gastrointestinal stromal tumor (GIST) with mast cell infiltrations: a subtype of GIST with mutations of platelet-derived growth factor receptor alpha gene", 35, pp.1223~1230 (2004)
- "Different inhibitory effect of imatinib on phosphorylation of mitogen-activated protein kinase and Akt and on proliferation in cells expressing different types of mutant platelet-derived growth factor receptor-", 111, pp.317~321 (2004)
- "Receptor tyrosine kinases expressed in metastatic colon cancer", 60, pp.791~797 (1995)