Increased Expression of Cyclin-Dependent Kinase-Interacting Protein p21 during Tamoxifen-Induced Hepatocarcinogenesis in Female Rats
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概要
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Female Sprague-Dawley rats were given a single dose of tamoxifen (20 mg/kg body weight) by gavage or the same dose at 24-hr intervals for 2, 12, or 52 weeks, and the altered expression of cyclin-dependent kinase-interacting protein p21 (p21), tumor suppression protein p53, and the placental form of glutathione S-transferase (GST-P) in the liver was comparatively examined during the process of tamoxifen-induced hepatocarcinogenesis. The development of hepatocellular carcinoma was histopathologically observed only in rats administered tamoxifen for 52 weeks, but not in any other experimental groups. Significant increases in levels of the mRNA and protein of p21 were first observed in rats administered tamoxifen for 2 weeks, and the levels increased with further long-term treatment. Immunohistochemical analyses of p21 and GST-P in the liver of rats administered tamoxifen for 12 and 52 weeks revealed that the localization of p21-positive cells did not necessarily coincide with that of GST-P-positive cells. In the 52-week group, p21-positive cells, rather than GST-P-positive cells, were observed preferentially in the region consisting of histopathologically malignant cells. The present study demonstrated that during the process of tamoxifen-induced hepatocarcinogenesis, expression levels of the mRNA and protein of p21 were increased. The significance of the increased expression of p21 during hepatocarcinogenesis is discussed.
- 公益社団法人日本薬学会の論文
- 2005-04-01
著者
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DEGAWA Masakuni
Department of Molecular Toxicology, School of Pharmaceutical Sciences, University of Shizuoka
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KASAHARA Toshihiko
Pharmaceutical Research Center
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KASAHARA Toshihiko
Department of Molecular Toxicology and COE Program in the 21st Century, School of Pharmaceutical Sci
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KUWAYAMA Chitose
Department of Pathology, Juntendo University School of Medicine
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HASHIBA Masamichi
Department of Molecular Toxicology and COE Program in the 21st Century, School of Pharmaceutical Sci
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HARADA Tsuyoshi
First Department of Biochemistry, Saitama Medical School
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KAKINUMA Chihaya
Department of Pathology, Juntendo University School of Medicine
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柿沼 千早
Toxicology Laboratory Mochida Pharmaceutical Co. Ltd.
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Kuwayama Chitose
Department Of Pathology Juntendo University School Of Medicine
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桑山 知登世
Toxicology Laboratory Mochida Pharmaceutical Co. Ltd.
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Hashiba Masamichi
Department Of Molecular Toxicology And The 21st Century Coe Program School Of Pharmaceutical Science
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Kasahara Toshihiko
Department Of Molecular Toxicology And The 21st Century Coe Program School Of Pharmaceutical Science
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Kasahara Toshihiko
Department Of Applied Biochemistry Hiroshima University
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Kakinuma Chihaya
Pharmaceutical Research Center
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Degawa Masakuni
Department Of Molecular Toxicology And The 21st Century Coe Program School Of Pharmaceutical Science
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Degawa Masakuni
Department Of Hygienic Chemistry Faculty Of Pharmaceutical Sciences Tohoku University
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Kuwayama Chitose
Pharmaceutical Research Center Mochida Pharmaceutical Co. Ltd
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Harada Tsuyoshi
Development Research Mochida Pharmaceutical Co. Ltd.
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柿沼 千早
Department of Pathology, Juntendo University, School of Medicine
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