2000 Fiscal Year Annual Research Report
| Project/Area Number |
09470244
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| Research Institution | FUKUSHIMA MEDICAL UNIVERSITY |
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Principal Investigator |
竹之下 誠一 福島県立医科大学, 医学部, 教授 (10167489)
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| Co-Investigator(Kenkyū-buntansha) |
宮園 浩平 東京大学, 大学院・医学系研究科, 教授 (90209908)
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| Keywords | TGF-β / Smad / 癌抑制遺伝子 / 増殖因子 / 遺伝子診断 |
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| Research Abstract |
対象遺伝子のヒトゲノム上の構造は、癌の臨床で行われるDNAを基質とした癌関連遺伝子の研究には不可欠なものである。我々は平成9年より、MAD関連遺伝子の構造決定と機能解析という研究課題の基に、TGF-βシグナル伝達系と癌との関連を明らかにするために、TGF-βシグナル伝達因子のなかのTGF-βII型受容体,Smad2 Smad3,Smad6,Smad7の遺伝子構造を決定し、様々な癌組織でのそれぞれの遺伝子異常の検討を行い報告してきた。今年度は、本プロジェクトの総括をした。
1.これまでにEMBL/GenBanKに登録した(Data Libraries under Accession Nos.)のは、
Smad2:U78726to U78733
Smad3:AF025293to AF025300,AB004922to AB004930
Smad4(promotor):U44378
Smad6:AF041062to AF041065
Smad7:AP026556to AF026559
2.今回解析したTGF-βシグナル伝達因子のうちヒトの癌組織で遺伝子変異を確認できたのはSmad4、Smad2、TGF-βII型とI型受容体だけで、Smad3、Smad6、Smad7での異常は無かった。
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[Publications] Wang D, et al: "Mutation analysis of the smad6 and smad7 gene in human ovarian cancers."International Journal of Oncology. 17(6). 1087-1091 (2000)
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[Publications] Osawa H, et al: "Mutation analysis of transforming growth factor beta type II receptor, smad2, smad3 and smad4 in esophageal squamous cell carcinoma."International Journal of Oncology. 17(4). 723-728 (2000)
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[Publications] Wang D, et al: "Analysis of specific gene mutations in the transforming growth factor-beta signal transduction pathway in human ovarian cancer."Cancer Reseach. 60(16). 4507-4512 (2000)
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[Publications] Yoshida Y, et al: "Negative Regulation of BMP/Smad Signaling by Tob in Osteoblasts."Cell. 103(7). 1085-1097 (2000)
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[Publications] Nishimori S, et al: "Smad-mediated transcription is required for TGF-beta 1-induced p57Kip2 proteolysis in osteoblastic cells."Journal of Biological Chemistry. (epub ahead of print). (2001)
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[Publications] Kanai H, et al: "Transforming growth factor-ss /Smads signaling induces transcription of the cell type-restricted ankyrin repeat protein CARP gene through CAGA motif in vascular smooth muscle cells."Circ.Reseach. 88(1). 30-36 (2001)
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[Publications] Miyazono K.: "Positive and negative regulation of TGF-beta signaling."J.Cell Sci.. 113(pt7). 1101-1109Review (2000)
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[Publications] Ishida W, et al: "Smad6 is a Smad1/5-induced smad inhibitor. Characterization of bone morphogenetic protein-responsive element in the mouse Smad6 promoter."Journal of Biological Chemistry. 275(9). 6075-6079 (2000)
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[Publications] Kusanagi K, et al: "Characterization of a bone morphogenetic protein-responsive Smad-binding element."Mol.Biol.Cell.. 11(2). 555-565 (2000)
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[Publications] Kawabata M, et al: "Intracellular signaling of the TGF-beta superfamily by Smad proteins."Ann.NY.Acad.Sci.. 886. 73-82Review (1999)
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[Publications] Ten Dijke P, et al: "Signaling inputs converge on nuclear effectors in TGF-beta signaling."Trends Biochem. Sci.. 25(2). 64-70Review (2000)
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[Publications] Tada K, et al: "Region between alpha-helices 3 and 4 of the mad homology 2 domain of Smad4: functional roles in oligomer formation and transcriptional activation."Genes Cells.. 4(12). 731-741 (1999)
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[Publications] Miura S, et al: "Hgs (Hrs), a FYVE domain protein, is involved in smad signaling through cooperation with SARA."Molecular Cell Biology. 20(24). 9346-9355 (2000)
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[Publications] Miyazono K.: "TGF-beta/SMAD signaling and its involvement in tumor progression."Biol.Pharm.Bull.. 23(10). 1125-1130 (2000)
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[Publications] Zhang YW, et al: "A RUNX2/PEBP2 alpha A/CBFA1 mutation displaying impaired transactivation and Smad interaction in cleidocranial dysplasia."Proc.Natl.Acad.Sci.USA.. 97(19). 10549-10554 (2000)
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[Publications] Udagawa Y, et al: "Schnurri interacts with Mad in a Dpp-dependent manner."Genes Cells. 5(5). 359-369 (2000)
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[Publications] Miyazono K, et al: "TGF-beta signaling by Smad proteins."Adv.Immunol.. 75. 115-157 (2000)
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[Publications] Miyazono K.: "TGF-beta signaling by Smad proteins."Cytokine Growth Factor Rev.. 11(1-2). 15-22Review (2000)
