Analysis of Gene Expression Profile on Uterine Tumorigenesis Initiated with N-ethyl-N-nitrosourea and Inhibited by Ethinylestradiol in rasH2 Mice
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概要
- 論文の詳細を見る
In order to clarify the possible mechanisms underlying the inhibition of uterine tumorigenesis in rasH2 mice carrying a human prototype c-Ha-ras gene when treated with ethinylestradiol (EE), mice were given a single intraperitoneal injection of 120 mg/kg N-ethyl-N-nitrosourea (ENU), followed by 2.5 ppm EE for 6 weeks. Many genes involved in estrogen responses and cell proliferation in the uterus of rasH2 mice are activated by treatment with ENU followed by EE. These include genes associated with receptors such as estrogen receptor (ER) alpha, cell cycles such as cyclin E, cyclin dependent kinase (CDK) 4, CDK inhibitors, ubiquitin and smad3, and growth factors such as epidermal growth factor (EGF) receptor, transforming growth factor (TGF) beta, TGF beta receptor and insulin-like growth factor (IGF). In this study, the ENU+EE treated rasH2 mice demonstrated acceleration of estrogen decomposition and down-regulation of the expression of ER alpha. TGF beta, serine/threonine kinase and smad3, which are downstream of the TGF beta signaling pathway, were also down-regulated, indicating signal values such as CDK4 were down-regulated in the ENU+EE treated rasH2 mice. Ubiquitin which indicates CDK inhibitory metabolism was also down-regulated. Finally, several genes involved in growth factors such as EGF receptor, TGF beta receptor and IGF were also down-regulated. On the other hand, the ENU+EE treated ICR mice showed deceleration of estrogen decomposition and up-regulation of the expression of ER alpha, down-regulation of TGF beta, serine/threonine kinase, smad3, CDK4, ubiquitin, EGF receptor, TGF beta receptor and IGF, indicating that these genes appear to act as stimulants of cell proliferation and carcinogenesis. Therefore, we consider that these genes are key genes which are strongly involved in the inhibition of uterine carcinogenesis in ENU-initiated rasH2 mice treated with EE.
- 日本毒性病理学会の論文
- 2004-09-30
著者
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MITSUMORI Kunitoshi
Laboratory of Veterinary Pathology, Tokyo University of Agriculture and Technology
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Mitsumori Kunitoshi
東京大学医科学研究所 癌細胞シグナル分野
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Mitsumori Kunitoshi
Toxicology Division Institute Of Environmental Toxicology
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WATANABE Takao
Laboratory of Veterinary Pathology, Tokyo University of Agriculture and Technology
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KASHIDA Yoko
Laboratory of Veterinary Pathology, Tokyo University of Agriculture and Technology
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Muto Tomoko
麻布大学 獣医学部比較毒性学
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武藤 朋子
Department Of Pharmacology And Toxicology Kyorin University School Of Medicine
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Muto Tomoko
Laboratory Of Veterinary Pathology Tokyo University Of Agriculture And Technology
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Muto Tomoko
Department Of Pharmacology And Toxicology Kyorin University School Of Medicine
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Muto Tomoko
Comparative Toxicology Laboratories Azabu University School Of Veterinary Medicine
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Yasuhara Kazuo
Divisions Of Toxicology National Institute Of Hygienic Sciences
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Yasuhara Kazuo
Division Of Pathology National Institute Of Health Sciences
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Watanabe Takao
Laboratory Of Veterinary Pathology Faculty Of Agriculture Tokyo University Of Agriculture And Techno
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SUMIDA Kayo
Environmental Health Science Laboratory, Sumitomo Chemical Co., Ltd
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WATANABE Tomoyuki
Corporate Planning & Coordination Office, Sumitomo Chemical Co., Ltd
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Kodama Yukio
Division Of Pathology National Institute Of Health Sciences
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Kitamura Y
Division Of Pathology National Institute Of Health Sciences
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安原 加壽雄
San-ei Gen F.f.i. Inc.
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Kurokawa Y
Division Of Toxicology National Institute Of Health Sciences
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Mitsumori Kunitoshi
Department Of Pathology National Institute Of Health Sciences
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Mitsumori Kunitoshi
Laboratory Of Veterinary Pathology Division Of Animal Science Institute Of Symbiotic Science And Tec
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Sumida Kayo
Environmental Health Science Laboratory Sumitomo Chemical Co. Ltd
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Kamimura Yasuhiro
Safety Evaluation Lab. Yoshitomi Pharm.
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Yoshikawa Katsunori
Department Of Bioinformatic Engineering Graduate School Of Information Science And Technology Osaka
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Matsumoto K
Kyushu Univ. Fukuoka Jpn
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Matsumoto K
Drug Safety Research Laboratories Pharmaceutical Research Division Takeda Chemical Industries Ltd.:l
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Kurokawa Y
Division Of Cellular & Molecular Toxicology National Institute Of Health Sciences
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Kodama Y
Biological Safety Research Center National Institute Of Health Science
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三森 国敏
Division Of Pathology National Institute Of Health Sciences
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Kawasaki Yasushi
National Institute Of Health Sciences
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Kashida Y
Laboratory Of Veterinary Pathology Tokyo University Of Agriculture And Technology
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Kodama Yukio
Cel. Mol. Tox. Div. Nihs
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Matsumoto K
Laboratory Of Veterinary Pathology Tokyo University Of Agriculture And Technology
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Watanabe Tomoyuki
Laboratory Of Veterinary Pathology Tokyo University Of Agriculture And Technology
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Katakura Yoshio
Department Of Life Science And Bioengineering Faculty Of Chemistry Materials And Bioengineering Kans
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Sumida Kayo
Environmental Health Sci. Lab. Sumitomo Chemical Co. Ltd.
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Yasuhara Kazuo
Division Of Toxicology Biological Safety Research Center National Institute Of Hygienic Sciences
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Katakura Yoshio
Department Of Biotechnology Faculty Of Engineering Osaka University
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