1996 年度実績報告書

転写制御遺伝子群の発癌への関与

研究課題

研究課題/領域番号	08264107
研究機関	九州大学
研究代表者	林健志九州大学, 遺伝情報実験施設, 教授 (00019671)
研究分担者	中別府雄作九州大学, 生体防御医学研究所, 助手 (30180350) 松田覚東京大学, 医科学研究所, 助手 (50242110) 森下和弘国立がんセンター研究所, 室長 (80260321) 濱田文彦大阪大学, 微生物研究所, 助手 (70252707) 恒吉正澄九州大学, 医学部, 教授 (10244229)
キーワード	hMTH1 / EVI-1 / Kid / p53 / 尿路腫瘍 / 平滑筋肉腫 / 転写因子YB-1 / 蛍光PCR-SSCP法
研究概要	1.hMTH1は、8-oxo-GTP分解酵素であり、突然変異頻度を抑制している。同酵素の遺伝子構造を決定し、択一的スプライシング機構によって数種類の酵素蛋白質が作られること、また、肺癌患者に、スプライシング異常を引き起こす生殖細胞突然変異を見い出した。2.がん抑制遺伝子であるWT1を、トランスフェクション後に強制的に発現誘導させたところ、細胞種によってその帰結が多様であることを見い出した。3.がん遺伝子c-erbB-2の発現調節に関与する転写因子様の蛋白質のcDNA2個を得た。このうちの一個、Kidは、セントロメア領域DNAとも結合し、染色体分配に深く関与していることを明らかにした。今一つのcDNA、tobは細胞増殖を抑制し、細胞周期にも関与することを示した。4.白血病原因遺伝子EVI-1のコードする蛋白質EVI-1のDrosophilahomologueを同定し、その機能を検索したところ、同蛋白質は神経系ニューロン形成の初期過程に関係していることが支唆された。5.平滑筋肉腫組織のp53遺伝子DNAを増幅し、変異配列を検索し、予後因子としての可能性を見い出した。尿路腫瘍の同時性および異時性多発例についての同様の解析では、多発例間で変異が一致するものとしないものがあり、多発性の原因には、モノクローナル、ポリクローナル2種のものがあると結論された。6.高分解能・高度自動化キャピラリー電気泳動装置による効率の良い蛍光PCR-SSCP法を確立した。この方法は、変異の判定を、コンピュータにより統計的根拠によって行うものであり、全過程における人的ミスの排除、検出感度の飛躍的向上を達成した。7.多剤耐性遺伝子の転写因子YB-1のc-DNAおよびゲノムDNAのクローニングを行い、シスプラチン耐性細胞におけるはYB-1の高発現、発現抑制によるシスプラチン感受性の増加を証明した。

研究成果

(39件)

すべてその他

すべて文献書誌 (39件)

[文献書誌] Nishizaka,H.: "Molecular bases for inherited human complement C6 deficiency in two unrelated individuals." J.Immunol.156. 2309-2315 (1996)
[文献書誌] Suzuki,J: "The expression of antibodies against HTLV-l pX-gene mutant products with HTLV-l-associated myelopathy(HAM)/tropical spastic paraparesis(TSP)" J.Infect.Deseases. 173. 1115-1122 (1996)
[文献書誌] Inazuka,M.: "One-tube post-PCR fluorescent labeling of DNA fragments" Genome Research. 6. 551-557 (1996)
[文献書誌] Kukita,Y.: "SSCP Analysis of Long DNA Fragments in Low pH Gel" Human Mutation,. (in press).
[文献書誌] Hirakawa,N.: "Over expression of bcl-2 protein in synovial sarcoma:a comparative study of the soft tissue spindle cell sarcomas and an additional analysis by fluorscence" Hum Pathol. 27. 1060-1065 (1996)
[文献書誌] Yao,T.: "p53 expression patterns in colorectal adenomas and early carcinomas:a special reference to depressed adenoma and non-polypoid carcinoma." Pathol Int. 46. 962-967 (1996)
[文献書誌] Nakamura,S.: "Inverse correlation between the expression of bcl-2 and p53 proteins in primary gastic lymphoma." Hum Pathol. 27. 225-233 (1996)
[文献書誌] Naka,T.: "Proliferative activities in conventional chordoma:a clinicopathologic,DNA flow cytometric,and immunohistochemical analysis of 17 specimens with special" Hum Pathol. 27. 381-388 (1996)
[文献書誌] Noguchi,S.: "Nuclear morphometry and the MIB-1 index in rhabdomyosarcoma. Mod" Pathol. 3. 253-260 (1996)
[文献書誌] Maeda,T.: "Proliferative activity in intrahepatic metastasis of hepatocellular carcinoma." J Gastroenterol and Hepatol. 11. 752-757 (1996)
[文献書誌] Maeda,T.: "Spindle cell hepatocellular carcinoma, a clinicopathologic and immunohistochemical analysis of 15 cases." Cancer. 77. 51-57 (1996)
[文献書誌] Maeda,T.: "The expression of cytokeratin 7,19,and 20 in primary and metastatic carcinoma of the liver." Mod Pathol. 9. 901-909 (1996)
[文献書誌] Adachi,E.: "Factors correlated with portal venous invasion by hepatocellular carcinoma,univariate and multivariate analyses of 232 resected cases without preoperative" Cancer. 77. 2022-2031 (1996)
[文献書誌] Yao,T.: "Gastric epithelioid stromal tumor(leimyoma)with granular changes." Int J Surg Pathol. 4. 37-42 (1996)
[文献書誌] Oya,M.: "Chronic irradiation enteritis:its correlation with the elapsing time interval and morphologic change." Hum Pathol. 27. 774-781 (1996)
[文献書誌] Nagai,E.: "Duodenal epithelial neoplasms complicating von Recklinghausen's disease,an immunohistochemical analysis in two patients." Int J Surg Pathl. 3. 229-240 (1996)
[文献書誌] Kawauti,S.: "Hemangiopericytoma of the ovary, a case report." Int J Surg Pathol. 4. 115-120 (1996)
[文献書誌] R.N.Bhattacharjee,: "The tumor suppressor gene product APC is hyperphosphorylated during the M phase." Biochem.Biophys.Res.Commun.220. 192-195 (1996)
[文献書誌] Taki,T.: "Fusion of the MLL gene with two different genes, AF-6 and AF-5a,by a complex translocation involving chromosomes 5,6,8,and 11 in infant leukemia." Oncogene. 13. 2121-2130 (1996)
[文献書誌] Nagashima,M.: "Presence of human celluar protein(s) that specifically binds and cleaves 8-hydroxyguanine containlg DNA." Mut.Res.(in press).
[文献書誌] Adachi,J.: "Induction of apoptosis but not G1 arrest by expression of the wild-type p53 gene in small cell lung carcinoma." Cell Growth & Differentiation. 7. 879-886 (1996)
[文献書誌] Asoh,H.: "Establishment of an undifferentiated leukemia cell line(Kasumi-3)with t(3;7)(q27;q22)and activation of the EVI1 gene." Jpn.J.Cancer Res.87. 269-274 (1996)
[文献書誌] Asho,H.: "Establishment of myeloid leukaemia cell line (Kasumi-4) with t(9;22;11)(q34;q11;q13),inv(3)(q21q26)and the EVI1 gene activation from a patient with" Br.J.Haematol.93. 68-74 (1996)
[文献書誌] Y.Yoshida,: "Cloning and characterization of the mouse tob gene." Gene,. (in press).
[文献書誌] S.Matsuda,: "Tob,a novel protein that interacts with p185erbB2,is associated with anti-proliferative activity." Oncogene,. 12. 705-713 (1996)
[文献書誌] S.Kuramochi,: "Molecular cloning and characterization of Byp,a murine receptor-type tyrosine phosphatase similar to human DEP-1." FEBS Letters,. 378. 7-14 (1996)
[文献書誌] N.Fusaki,: "Physical and functional interactions of protein tyrosine kinase,p59fyn and ZAP-70,in T cell signalling." J.Immunol.156. 1369-1677 (1996)
[文献書誌] M.Onda,: "ErbB-2 expression is correlated with poor prognosis in osteosarcoma." Cancer,. 77. 71-78 (1996)
[文献書誌] F.Vahid-Ansari,: "SeroquelTM and Haloperidol Administration on DFosB-like Immunoreactivity in the Forebrain." European J. Neuroscience. 8. 927-936 (1996)
[文献書誌] J.-P. Doucet,: "Chronic alteration in dopaminergic neuro-transmission produce a persistent elevation of DFosB-like protein(s) in both the rodent and primate striatum." European J. Neuroscience. 8. 365-381 (1996)
[文献書誌] A.Taketomi,: "Requirement of two conserved cysteine residues of Ada protein of Escherichia coli for transactivation of ada promoter." Mol.Gen.Genet.250. 523-532 (1996)
[文献書誌] R.Shimizu,: "Role of c-jun in the inhibition of apoptosis through the erythropoietin receptor." Biochem.Biophys.Res.Commun.222. 1-6 (1996)
[文献書誌] Y.Yamagata,: "Three-Dimensional Structure of a DNA Repair Enzyme,3-Methyladenine DNA Glycosylase II,from Escherichia coli." Cell. 86. 311-319 (1996)
[文献書誌] H.Maki,: "DNA Replication and Transcription." Encyclopedia of Molecular Molecular Biology and Medicine.VCH Publishers Inc.New York.86-96 (1996)
[文献書誌] M.Sekiguchi,: "DNA repair methyltransferase as a molecular device for preventing mutation and cancer." J.Cancer Res.Oncol.Clin.122. 199-206 (1996)
[文献書誌] T.Ohga,: "Role of the human Y box-binding protein YB-1 in cellular sensitivity to the DNA-damaging agents cisplatin,mitomycin C,and ultraviolet light." Cancer Res.56. 4224-4228 (1996)
[文献書誌] Y.Makino,: "Structural and functional analysis of the human Y-box binding protein(YB-1)gene promoter." Nucleic Acids Research,. 24. 1873-1878 (1996)
[文献書誌] Hayashi,K.: "PCR-SSCP" Laboratory Protocol for Mutation Detection,Landegren,U.ed, 8 (1996)
[文献書誌] Hayashi,K.: "Single strand conformation polymorphism analysis" Mutation Detection:A Practical Approach",S.M.Forrest and R.G.H.Cotton eds(in press),

1996 年度 実績報告書

転写制御遺伝子群の発癌への関与

研究代表者

林 健志 九州大学, 遺伝情報実験施設, 教授 (00019671)

研究成果

[文献書誌] Nishizaka,H.: "Molecular bases for inherited human complement C6 deficiency in two unrelated individuals." J.Immunol.156. 2309-2315 (1996)

[文献書誌] Suzuki,J: "The expression of antibodies against HTLV-l pX-gene mutant products with HTLV-l-associated myelopathy(HAM)/tropical spastic paraparesis(TSP)" J.Infect.Deseases. 173. 1115-1122 (1996)

[文献書誌] Inazuka,M.: "One-tube post-PCR fluorescent labeling of DNA fragments" Genome Research. 6. 551-557 (1996)

[文献書誌] Kukita,Y.: "SSCP Analysis of Long DNA Fragments in Low pH Gel" Human Mutation,. (in press).

[文献書誌] Hirakawa,N.: "Over expression of bcl-2 protein in synovial sarcoma:a comparative study of the soft tissue spindle cell sarcomas and an additional analysis by fluorscence" Hum Pathol. 27. 1060-1065 (1996)

[文献書誌] Yao,T.: "p53 expression patterns in colorectal adenomas and early carcinomas:a special reference to depressed adenoma and non-polypoid carcinoma." Pathol Int. 46. 962-967 (1996)

[文献書誌] Nakamura,S.: "Inverse correlation between the expression of bcl-2 and p53 proteins in primary gastic lymphoma." Hum Pathol. 27. 225-233 (1996)

[文献書誌] Naka,T.: "Proliferative activities in conventional chordoma:a clinicopathologic,DNA flow cytometric,and immunohistochemical analysis of 17 specimens with special" Hum Pathol. 27. 381-388 (1996)

[文献書誌] Noguchi,S.: "Nuclear morphometry and the MIB-1 index in rhabdomyosarcoma. Mod" Pathol. 3. 253-260 (1996)

[文献書誌] Maeda,T.: "Proliferative activity in intrahepatic metastasis of hepatocellular carcinoma." J Gastroenterol and Hepatol. 11. 752-757 (1996)

[文献書誌] Maeda,T.: "Spindle cell hepatocellular carcinoma, a clinicopathologic and immunohistochemical analysis of 15 cases." Cancer. 77. 51-57 (1996)

[文献書誌] Maeda,T.: "The expression of cytokeratin 7,19,and 20 in primary and metastatic carcinoma of the liver." Mod Pathol. 9. 901-909 (1996)

[文献書誌] Adachi,E.: "Factors correlated with portal venous invasion by hepatocellular carcinoma,univariate and multivariate analyses of 232 resected cases without preoperative" Cancer. 77. 2022-2031 (1996)

[文献書誌] Yao,T.: "Gastric epithelioid stromal tumor(leimyoma)with granular changes." Int J Surg Pathol. 4. 37-42 (1996)

[文献書誌] Oya,M.: "Chronic irradiation enteritis:its correlation with the elapsing time interval and morphologic change." Hum Pathol. 27. 774-781 (1996)

[文献書誌] Nagai,E.: "Duodenal epithelial neoplasms complicating von Recklinghausen's disease,an immunohistochemical analysis in two patients." Int J Surg Pathl. 3. 229-240 (1996)

[文献書誌] Kawauti,S.: "Hemangiopericytoma of the ovary, a case report." Int J Surg Pathol. 4. 115-120 (1996)

[文献書誌] R.N.Bhattacharjee,: "The tumor suppressor gene product APC is hyperphosphorylated during the M phase." Biochem.Biophys.Res.Commun.220. 192-195 (1996)

[文献書誌] Taki,T.: "Fusion of the MLL gene with two different genes, AF-6 and AF-5a,by a complex translocation involving chromosomes 5,6,8,and 11 in infant leukemia." Oncogene. 13. 2121-2130 (1996)

[文献書誌] Nagashima,M.: "Presence of human celluar protein(s) that specifically binds and cleaves 8-hydroxyguanine containlg DNA." Mut.Res.(in press).

[文献書誌] Adachi,J.: "Induction of apoptosis but not G1 arrest by expression of the wild-type p53 gene in small cell lung carcinoma." Cell Growth & Differentiation. 7. 879-886 (1996)

[文献書誌] Asoh,H.: "Establishment of an undifferentiated leukemia cell line(Kasumi-3)with t(3;7)(q27;q22)and activation of the EVI1 gene." Jpn.J.Cancer Res.87. 269-274 (1996)

[文献書誌] Asho,H.: "Establishment of myeloid leukaemia cell line (Kasumi-4) with t(9;22;11)(q34;q11;q13),inv(3)(q21q26)and the EVI1 gene activation from a patient with" Br.J.Haematol.93. 68-74 (1996)

[文献書誌] Y.Yoshida,: "Cloning and characterization of the mouse tob gene." Gene,. (in press).

[文献書誌] S.Matsuda,: "Tob,a novel protein that interacts with p185erbB2,is associated with anti-proliferative activity." Oncogene,. 12. 705-713 (1996)

[文献書誌] S.Kuramochi,: "Molecular cloning and characterization of Byp,a murine receptor-type tyrosine phosphatase similar to human DEP-1." FEBS Letters,. 378. 7-14 (1996)

[文献書誌] N.Fusaki,: "Physical and functional interactions of protein tyrosine kinase,p59fyn and ZAP-70,in T cell signalling." J.Immunol.156. 1369-1677 (1996)

[文献書誌] M.Onda,: "ErbB-2 expression is correlated with poor prognosis in osteosarcoma." Cancer,. 77. 71-78 (1996)

[文献書誌] F.Vahid-Ansari,: "SeroquelTM and Haloperidol Administration on DFosB-like Immunoreactivity in the Forebrain." European J. Neuroscience. 8. 927-936 (1996)

[文献書誌] J.-P. Doucet,: "Chronic alteration in dopaminergic neuro-transmission produce a persistent elevation of DFosB-like protein(s) in both the rodent and primate striatum." European J. Neuroscience. 8. 365-381 (1996)

[文献書誌] A.Taketomi,: "Requirement of two conserved cysteine residues of Ada protein of Escherichia coli for transactivation of ada promoter." Mol.Gen.Genet.250. 523-532 (1996)

[文献書誌] R.Shimizu,: "Role of c-jun in the inhibition of apoptosis through the erythropoietin receptor." Biochem.Biophys.Res.Commun.222. 1-6 (1996)

[文献書誌] Y.Yamagata,: "Three-Dimensional Structure of a DNA Repair Enzyme,3-Methyladenine DNA Glycosylase II,from Escherichia coli." Cell. 86. 311-319 (1996)

[文献書誌] H.Maki,: "DNA Replication and Transcription." Encyclopedia of Molecular Molecular Biology and Medicine.VCH Publishers Inc.New York.86-96 (1996)

[文献書誌] M.Sekiguchi,: "DNA repair methyltransferase as a molecular device for preventing mutation and cancer." J.Cancer Res.Oncol.Clin.122. 199-206 (1996)

[文献書誌] T.Ohga,: "Role of the human Y box-binding protein YB-1 in cellular sensitivity to the DNA-damaging agents cisplatin,mitomycin C,and ultraviolet light." Cancer Res.56. 4224-4228 (1996)

[文献書誌] Y.Makino,: "Structural and functional analysis of the human Y-box binding protein(YB-1)gene promoter." Nucleic Acids Research,. 24. 1873-1878 (1996)

[文献書誌] Hayashi,K.: "PCR-SSCP" Laboratory Protocol for Mutation Detection,Landegren,U.ed, 8 (1996)

[文献書誌] Hayashi,K.: "Single strand conformation polymorphism analysis" Mutation Detection:A Practical Approach",S.M.Forrest and R.G.H.Cotton eds(in press),

1996 年度実績報告書

林健志九州大学, 遺伝情報実験施設, 教授 (00019671)