1995 Fiscal Year Annual Research Report

転写制御遺伝子群の発癌への関与

Research Project

Project/Area Number	07272108
Research Institution	Kyushu University
Principal Investigator	林健志九州大学, 遺伝情報実験施設, 教授 (00019671)
Co-Investigator(Kenkyū-buntansha)	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) 常吉正澄九州大学, 医学部, 教授 (10244229)
Keywords	蛍光標識PCR-SSCP法 / 軟部悪性腫瘍 / がん遺伝子EVI-1 / △FosB / がん抑制遺伝子WT1 / がん遺伝子c-erbB-2
Research Abstract	発癌に関与する転写遺伝子群の作用機構に関わる数多くの遺伝子群を同定した。またこれらの遺伝子群の臨床的な癌における構造異常検索を行い、かつより多くの遺伝子構造異常検索のための実験系の確立に着実な成果をあげた。浜田は、転写関連の遺伝子で、かつがん抑制遺伝子であるWT1と相互作用する蛋白質のcDNAを酵母two hybrid法を用いて単離し、その性質を明らかにし、またWT1の白血病細胞増殖抑制作用を見いだした。中別府は、核内がん遺伝子産物△FosBがmRNAの安定化という新しいメカニズムによってサイクリンEとそのパートナーであるCDK2の発現を増加させ、細胞周期の回転、すなわち細胞増殖を引き起こし、これが細胞癌化を引き起こしうることを見いだした。松田は、がん遺伝子c-erbB-2の発現調節に関与すると思われる転写因子様の蛋白質のcDNA2個をサウスウェスタン法によってクローニングした。このうちの一個(toblと命名した)は細胞増殖抑制遺伝子btglと相同性を示すものであった。これ自身、細胞の増殖を抑制したが、この阻害は細胞周期依存的であり、CDK4等との相互作用によることを見い出した。森下は白血病原因遺伝子EVI-1の持つ2個のDNA結合領域はGATA/ETS結合領域と類似しており、これらの転写因子と相互作用することにより癌化を引き起こすと結論した。恒吉はホルマリン固定パラフィン包埋標本から効率よく標的DNAを増幅し、変異配列を検索する実験法を確立し、これを利用して平滑筋肉腫、大腸癌各数十例でのp53の異常を検索した。またこの結果と臨床病理学的データ、およびp53蛋白質の免疫染色の結果を総合し、診断への応用について検討した。林は遺伝子構造異常の大規模検索法として、PCRチューブ内での極めて単純な操作のみで行える増幅産物のポストPCR蛍光標識法を開発し、さらにキャピラリー電気泳動式DNAシークエンサーを用いた高度に自動化された非RIのPCR-SSCP法を確立した。さらに白血病細胞におけるp53遺伝子の突然変異検出に極めて有効であることを示し、今後臨床診断としてのDNA診断の実現にとって極めて重要な技術革新である。

Research Products
(39 results)

All Other

All Publications (39 results)

[Publications] Kawamura, M.: "Mutations of the p53 and ras genes in childhood t(1:19)-acute lymphoblastic leukemia" Blood. 85. 2546-2552 (1995)
[Publications] Sugano, K.: "Single-strand conformation polymorphism analysis by perpendicular temperature gradient get electrophoresis" Electrophoresis. 16. 8-10 (1995)
[Publications] Yasuda, J.: "Cloning and characterization of rat cellular nucleic acid binding protein (CNBP) cDNA" DNA Research. 2. 45-49 (1995)
[Publications] Shibata, H.: "RNA-primed PCR" Gemome Research. 5. 400-403 (1995)
[Publications] Myers, R. M.: "Detection of Mutations" “Genome Analysis: A Laboratory Manual",. (in press).
[Publications] Nishizaka, H.: "Molecular bases for inherited human complement C6 deficiency in two unrelated individuals" J. Immunol.(in press).
[Publications] Munakata, N.: "Gene music" “Visualizing Biological Information",. (in press).
[Publications] Hayashi, K.: "PCR-SSCP" “Mutation Detection",. (in press).
[Publications] Suzuki, J.: "The expression of antibodies against HTLV-I pX-gene mutant products with HTLV-I associated myelopathy (HAM)/tropical spastic paraparesis(TSP)" J. Infect. Desease,. (in press).
[Publications] Oya, M.: "Metastasizing Intramucosal Gastric Carcinomas Well Differentiated Type and Proliferative Activity Using Proliferative Cell" Cancer. 75. (1995)
[Publications] Oshiro, Y.: "Atypical Fibroxanthoma versus Benign and Malignant Fibrous Histiocytoma: A Comparative Study of their Proliferative Activity Using MIB-I, DNA Flow" Cancer. 75. (1995)
[Publications] Adachi, E.: "Risk Factors for Intrahepatic Recurrence in Human Small Hepatocellular Carcinoma" Am. Gastroenterol. Association. 108. 768-775 (1995)
[Publications] Amada, S.: "Leiomyosarcoma Versus Bizarre and Cellular Leiomyomas of the Uterus: A Comparative Study Based on the MIB-1 and" Int. J. Gynecological Pathology. 14. 134-142 (1995)
[Publications] Nagai, E.: "Intraductal Papillary Mucinous Neoplasms of the Pancreas Associated with So-called Mucinous Ductal Ectasia" Am. J. Surgical Pathology. 19. 576-589 (1995)
[Publications] Yao, T.: "An Intestinal Counterpart of Pyogenic Granuloma of the Skin A Newly Proposed Entity" Am. J. Surgical Pathology. 19. 1054-1060 (1995)
[Publications] Maeda, T.: "Combined Hepatocellular and Cholangiocarcinoma: Proposed Criteria According to Cytokeratin Expression and Analysis of" Human Pathology. 26. 956-964 (1995)
[Publications] Maeda, T.: "Small Hepatocellular Carcinoma of Single Nodular Type: A Specific Reference to Its Surrounding Cancerous Area Undetected Radiologically and Macroscopically" J. Surgical Oncol.60. 75-79 (1995)
[Publications] Naka, T.: "Osteosarcoma versus Malignant Fibrous Histicytoma of Bone in Patients Older than 40 Years" Cancer. 76. 972-984 (1995)
[Publications] Nakamura, S.: "Primary Gastric Lymphoma A Clinicopathologic Study of 233 Gases with Special Reference to Evaluation with" Cancer. 76. 1313-1324 (1995)
[Publications] Ueki, T.: "Expression of basic fibroblast growth factor and fibroblast growth factor receptor in advanced gastric carcinoma" J. pathology. 177. 353-361 (1995)
[Publications] Maeda, T.: "CD34 expression in endothelial cells fo small hepatocellular carcinoma: Its correlation with tumour progression and angiographic findings" J. Gastroenterol. Hepatol.10. 650-654 (1995)
[Publications] Oda, Y.: "A Comparative Study of Nuclear Morphometry and Proliferating Activity in Neuroectodermal Tumors of Bone and Ewing's Sarcoma of Bone" Gen. Diagn. Pathol. 141. 121-129 (1995)
[Publications] Asou, H.: "Establishment of a myeloid leukemia cell line (Kasumi-4) with t(9;22;11), inv(3)(q21q26)and the EVI1 gene activation from a patient with chronic" British J. Haematol.(in press).
[Publications] Morishita, K.: "EVII zinc finger protein works as a transcriptional activator via binding to a consensus sequence of GACAAGATAAGATAA N 1-28 CTCATCTTC" Oncogene. 10. 1961-1967 (1995)
[Publications] Suzukawa,K.: "The human thrombopoietin gene is located on chromosome 3q26.33-q27,but is not transcriptionally aactivated in leukemia cells with 3q21 and 3q26" Leukemia. 9. 1328-1331 (1995)
[Publications] Matsuda, S.: "Tob,a novel protein that interacts with p185erbB2, is associated with antiproliferative activity" Oncogene. (in press).
[Publications] Onda, M.: "ErbB-2 expression is correlated with poor prognosis in osteosarcoma" Cancer. (in press).
[Publications] Fusaki, N.: "Physical and functional interactions of protein tyrosine kinases,p59fyn and ZAP70, in T cell signalling" J. Immunol.(in press).
[Publications] Kuramochi, S.: "Molecular cloning and characterization of Byp, a murine receptor-type tyrosine phosphatase similar to human DEP-1" FEBS Lett.378. 7-14 (1996)
[Publications] Watanabe, N.: "Expression of c-terminal src kinase in human colorectal cancer cell lines" Jpn. J. Clin. Oncol.25. 5-9 (1995)
[Publications] Oda, S.: "Stabilization of cyclin E and cdk2 mRNAs at Gl/S transition in Rat-1A cells emerging from the G0 state" Oncogene. 10. 1341-1351 (1995)
[Publications] Tanaka, K.: "Cyclic AMP-regulated Synthesis of the Tissue Inhibitors of Metalloproteinases Suppesses the Invasive Potential of the Human Fibrosarcoma Cell Line HT1080" Cancer Research. 55. 2927-2935 (1995)
[Publications] Kang, D.: "Intracellular Localiaztion of 8-Oxo-dGTPase in Human Cells, with Special Reference to the Role of the Enzyme in Mitochondria" J. Biol. Chem.270. 14659-14665 (1995)
[Publications] Tsuji, Y.: "FER-1, an enhancer of the ferritin H gene and a target of E1A-mediated transcriptional repression" Mol. Cell. Biol.15. 5152-5164 (1995)
[Publications] C.Wu: "Polymorphisms and probable lack of mutation in humaan mutT homolog, hMTHl, in hereditary nonpolyposis colorectal cancer" Biochem. Biophys. Res. Commun.214. 1239-1245 (1995)
[Publications] Chen. J.: "Regulation of DFosB and FosB-like proteins by electroconvulsive seizure(ECS) and cocaine treatments" Mol. Pharmacol.48. 880-889 (1995)
[Publications] Doucet, J. -P.: "Chronic alteration in dopaminergic neurotransmission produce a persistent elevation of DFosB-like protein(s) in both the rodent and primate striatum" European J. Neuroscience. (in press).
[Publications] Taketomi, A.: "Requirement of two conserved cysteine residues of Ada protein of Escherichia coli for transactivation of ada promoter" Mol. Gen. Genet.(in press).
[Publications] Otsuka, M.: "Polymorphism in the human O6-methylguanine-DNA methyltransferase gene detected by PCR-SSCP analysis" Pharmacogenetics. (in press).

1995 Fiscal Year Annual Research Report

転写制御遺伝子群の発癌への関与

Principal Investigator

林 健志 九州大学, 遺伝情報実験施設, 教授 (00019671)

Research Products

[Publications] Kawamura, M.: "Mutations of the p53 and ras genes in childhood t(1:19)-acute lymphoblastic leukemia" Blood. 85. 2546-2552 (1995)

[Publications] Sugano, K.: "Single-strand conformation polymorphism analysis by perpendicular temperature gradient get electrophoresis" Electrophoresis. 16. 8-10 (1995)

[Publications] Yasuda, J.: "Cloning and characterization of rat cellular nucleic acid binding protein (CNBP) cDNA" DNA Research. 2. 45-49 (1995)

[Publications] Shibata, H.: "RNA-primed PCR" Gemome Research. 5. 400-403 (1995)

[Publications] Myers, R. M.: "Detection of Mutations" “Genome Analysis: A Laboratory Manual",. (in press).

[Publications] Nishizaka, H.: "Molecular bases for inherited human complement C6 deficiency in two unrelated individuals" J. Immunol.(in press).

[Publications] Munakata, N.: "Gene music" “Visualizing Biological Information",. (in press).

[Publications] Hayashi, K.: "PCR-SSCP" “Mutation Detection",. (in press).

[Publications] Suzuki, J.: "The expression of antibodies against HTLV-I pX-gene mutant products with HTLV-I associated myelopathy (HAM)/tropical spastic paraparesis(TSP)" J. Infect. Desease,. (in press).

[Publications] Oya, M.: "Metastasizing Intramucosal Gastric Carcinomas Well Differentiated Type and Proliferative Activity Using Proliferative Cell" Cancer. 75. (1995)

[Publications] Oshiro, Y.: "Atypical Fibroxanthoma versus Benign and Malignant Fibrous Histiocytoma: A Comparative Study of their Proliferative Activity Using MIB-I, DNA Flow" Cancer. 75. (1995)

[Publications] Adachi, E.: "Risk Factors for Intrahepatic Recurrence in Human Small Hepatocellular Carcinoma" Am. Gastroenterol. Association. 108. 768-775 (1995)

[Publications] Amada, S.: "Leiomyosarcoma Versus Bizarre and Cellular Leiomyomas of the Uterus: A Comparative Study Based on the MIB-1 and" Int. J. Gynecological Pathology. 14. 134-142 (1995)

[Publications] Nagai, E.: "Intraductal Papillary Mucinous Neoplasms of the Pancreas Associated with So-called Mucinous Ductal Ectasia" Am. J. Surgical Pathology. 19. 576-589 (1995)

[Publications] Yao, T.: "An Intestinal Counterpart of Pyogenic Granuloma of the Skin A Newly Proposed Entity" Am. J. Surgical Pathology. 19. 1054-1060 (1995)

[Publications] Maeda, T.: "Combined Hepatocellular and Cholangiocarcinoma: Proposed Criteria According to Cytokeratin Expression and Analysis of" Human Pathology. 26. 956-964 (1995)

[Publications] Maeda, T.: "Small Hepatocellular Carcinoma of Single Nodular Type: A Specific Reference to Its Surrounding Cancerous Area Undetected Radiologically and Macroscopically" J. Surgical Oncol.60. 75-79 (1995)

[Publications] Naka, T.: "Osteosarcoma versus Malignant Fibrous Histicytoma of Bone in Patients Older than 40 Years" Cancer. 76. 972-984 (1995)

[Publications] Nakamura, S.: "Primary Gastric Lymphoma A Clinicopathologic Study of 233 Gases with Special Reference to Evaluation with" Cancer. 76. 1313-1324 (1995)

[Publications] Ueki, T.: "Expression of basic fibroblast growth factor and fibroblast growth factor receptor in advanced gastric carcinoma" J. pathology. 177. 353-361 (1995)

[Publications] Maeda, T.: "CD34 expression in endothelial cells fo small hepatocellular carcinoma: Its correlation with tumour progression and angiographic findings" J. Gastroenterol. Hepatol.10. 650-654 (1995)

[Publications] Oda, Y.: "A Comparative Study of Nuclear Morphometry and Proliferating Activity in Neuroectodermal Tumors of Bone and Ewing's Sarcoma of Bone" Gen. Diagn. Pathol. 141. 121-129 (1995)

[Publications] Asou, H.: "Establishment of a myeloid leukemia cell line (Kasumi-4) with t(9;22;11), inv(3)(q21q26)and the EVI1 gene activation from a patient with chronic" British J. Haematol.(in press).

[Publications] Morishita, K.: "EVII zinc finger protein works as a transcriptional activator via binding to a consensus sequence of GACAAGATAAGATAA N 1-28 CTCATCTTC" Oncogene. 10. 1961-1967 (1995)

[Publications] Suzukawa,K.: "The human thrombopoietin gene is located on chromosome 3q26.33-q27,but is not transcriptionally aactivated in leukemia cells with 3q21 and 3q26" Leukemia. 9. 1328-1331 (1995)

[Publications] Matsuda, S.: "Tob,a novel protein that interacts with p185erbB2, is associated with antiproliferative activity" Oncogene. (in press).

[Publications] Onda, M.: "ErbB-2 expression is correlated with poor prognosis in osteosarcoma" Cancer. (in press).

[Publications] Fusaki, N.: "Physical and functional interactions of protein tyrosine kinases,p59fyn and ZAP70, in T cell signalling" J. Immunol.(in press).

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

[Publications] Watanabe, N.: "Expression of c-terminal src kinase in human colorectal cancer cell lines" Jpn. J. Clin. Oncol.25. 5-9 (1995)

[Publications] Oda, S.: "Stabilization of cyclin E and cdk2 mRNAs at Gl/S transition in Rat-1A cells emerging from the G0 state" Oncogene. 10. 1341-1351 (1995)

[Publications] Tanaka, K.: "Cyclic AMP-regulated Synthesis of the Tissue Inhibitors of Metalloproteinases Suppesses the Invasive Potential of the Human Fibrosarcoma Cell Line HT1080" Cancer Research. 55. 2927-2935 (1995)

[Publications] Kang, D.: "Intracellular Localiaztion of 8-Oxo-dGTPase in Human Cells, with Special Reference to the Role of the Enzyme in Mitochondria" J. Biol. Chem.270. 14659-14665 (1995)

[Publications] Tsuji, Y.: "FER-1, an enhancer of the ferritin H gene and a target of E1A-mediated transcriptional repression" Mol. Cell. Biol.15. 5152-5164 (1995)

[Publications] C.Wu: "Polymorphisms and probable lack of mutation in humaan mutT homolog, hMTHl, in hereditary nonpolyposis colorectal cancer" Biochem. Biophys. Res. Commun.214. 1239-1245 (1995)

[Publications] Chen. J.: "Regulation of DFosB and FosB-like proteins by electroconvulsive seizure(ECS) and cocaine treatments" Mol. Pharmacol.48. 880-889 (1995)

[Publications] Doucet, J. -P.: "Chronic alteration in dopaminergic neurotransmission produce a persistent elevation of DFosB-like protein(s) in both the rodent and primate striatum" European J. Neuroscience. (in press).

[Publications] Taketomi, A.: "Requirement of two conserved cysteine residues of Ada protein of Escherichia coli for transactivation of ada promoter" Mol. Gen. Genet.(in press).

[Publications] Otsuka, M.: "Polymorphism in the human O6-methylguanine-DNA methyltransferase gene detected by PCR-SSCP analysis" Pharmacogenetics. (in press).

林健志九州大学, 遺伝情報実験施設, 教授 (00019671)