1994 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	06280115
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)	恒吉正澄九州大学, 医学部, 教授 (10244229) 森下和弘国立がんセンター研究所, 主任研究官 (80260321) 松田覚東京大学, 医科学研究所, 助手 (50242110) 佐藤明東京大学, 医学部, 助手 (70196210) 中別府雄作九州大学, 生体防御医学研究所, 助手 (30180350)
Keywords	蛍光標識PCR-SSCP法 / 軟部悪性腫瘍 / がん遺伝子EVI-1 / Zink finger / △FosB / がん抑制遺伝子WT1 / がん遺伝子c-erbB-2
Research Abstract	各班員はそれぞれの実験系を用いて、発癌に関与する転写遺伝子群の作用機構を解明し、これに関わる他の遺伝子群を数多く同定した。またこれらの遺伝子群の癌化における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。即ち、中別府は、核内がん遺伝子fosBの産物の一つである△FosBがサイクリンEとそのパートナーであるCDK2の発現をmRNA安定化によって増加させ、細胞増殖を引き起こすことを見いだした。佐藤は、がん抑制遺伝子WT1が細胞のG1/S移行を阻害し、またEC細胞の分化に抑制的に働き、血球系幹細胞と急性白血病細胞で異常発現してい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。一個はZink fingerを15個含む転写因子様蛋白質をコードし、今一個は細胞増殖抑制遺伝子btg1と相同性を示し、核移行シグナルと、PQの繰り返しを含むもので、これ自身、導入細胞の増殖を抑制した。森下は白血病原因遺伝子EVI-1の持つ2個のDNA結合領域の結合配列特異性を詳細に検討し、転写の活性化と抑制の両側面にそれぞれ関与していることを明らかにした。さらにこの蛋白質によって発現制御を受ける遺伝子の同定を進めている。恒吉は軟部悪性腫瘍(肉腫)における遺伝子構造異常を検索するためにホルマリン固定パラフィン包埋標本からの標的DNAの効率よいPCR増幅条件の検討を行ない、PCR-SSCP法によってすでに2例のp53点突然変異を同定している。またこれらの異常と、病理学的知見との相関に関して多くの知見を得ている。林は遺伝子構造異常の大規模検索法として、ポストラベル法による蛍光標識PCR-SSCP法の開発を行い、従来法の欠点であった蛍光標識プライマーの合成を経由しない実験法を確立した。

Research Products

(29 results)

All Other

All Publications (29 results)

[Publications] Gunji,T.: "Specific detection of positive and negative stranded hepatitis C viral RNA using chemical RNA modification" Arch.Virol.134. 293-302 (1994)
[Publications] Iizuka,M.: "Mapping of 28(CA)n microsatellite repeats and 13 Alu markers on human chromosome 11 using a panel of somatic cell hybrids" Genomics. 19. 581-584 (1994)
[Publications] Munakata,N.: "Molecular characterization of thirteen gyrA mutations conferring nalidisxic acid resistance in Bacillus subtilis" Mol.Gen.Genet.244. 97-103 (1994)
[Publications] Sachse,R.: "DNA aberrations at the retinoblastoma gene locus in human squamous cell carcinomas of the lung" Oncogene. 9. 39-47 (1994)
[Publications] Yashima,K.: "Mutations of the adenomatous polyposis coli gene in the mutation cluster region:Comparison of human pancreatic and colorectal cancer" Int.J.Cancer. 59. 43-47 (1994)
[Publications] Furihata,C.: "Induction of c-fos and c-myc oncogene in the pyrolic mucosa of rat stomach by N-methyl-N'-nitro-N-nitrosoguanidine and taurocholate" Cancer Letters. 83. 215-220 (1994)
[Publications] Iizuka,M.: "Twelve simple repeat sequence polymorphisms on chromosome 11,4,16 and 21" Hum.Molec.Genet.3. 1707-1708 (1994)
[Publications] Makino,R.: "Cloning and characterization of a c-myc intron binding protein (MIBP1)" Nucleic Acids Res.22. 5679-5685 (1994)
[Publications] Kawamura,M.: "Mutations of the p53 and ras genes in childhood t(1:19)-acute lymphoblastic leukemia" Blood. (in press).
[Publications] Sugano,K.: "Single-strand conformation polymorphism analysis by perpendicular temperature-gradient gel electrophoresis" Electrophoresis. 16. 8-10 (1995)
[Publications] Yasuda,J.: "Cloning and characterization of rat cellular nucleic acid binding protein (CNBP) cDNA" DNA Research,. (in press).
[Publications] Kohno,T.: "Homozygous deletion at chromosome 2q33 in human small-cell lung carcinoma identified by arbitrarily primed PCR genomic finger printing" Oncogene. 9. 103-108 (1994)
[Publications] Levy,E.R.: "DNA rearrangements distal to the Evi-1 locus associated with 3q21q26 syndrome" Blood. 83. 1348-1352 (1994)
[Publications] Suzukawa,K: "Identification of a breakpoint cluster region 3' of the ribophorin I gene at 3q21 associated with the transcriptional activation of the EVI-1 gene in acute" Blood. 84. 2681-2688 (1994)
[Publications] Ohyashiki,K.: "EVI1 expression associated with a 3q26 anomaly in a leukemia cell line derived from the blast crisis of chronic myeloid leukemia" Leukemia. 8. 2169-2173 (1994)
[Publications] Morishita,K.: "EVI-1 zinc finger protein works as a transcriptional activator via binding to a consensus sequence of GACAAGATAAGATAAN1-28 CTCATCTTC." Oncogene. (in press).
[Publications] Nagata,K.: "Solution structure of the epidermal growth factor like domain of helegulin-,a ligand for p180 erbB-4" EMBOJ.13. 3517-3523 (1994)
[Publications] Fusaki,N.: "Characterization of p59fyn-mediated signal transduction on T cell activation" International Immunology. 6. 1245-1255 (1994)
[Publications] Iyama,A.: "A unique structural feature of rabbit DNA repair methyltransferase as revealed by cDNA cloning" Carcinogenesis. 15. 627-663 (1994)
[Publications] Ishibashi,T.: "Artificial control of nuclear translocation of DNA repair methyltransferase" J.Biol.Chem.269. 7645-7650 (1994)
[Publications] Ishibashi,T.: "Intracellular localization and function of DNA repair methyltransferase in human cells" Mutation Res. 315. 199-212 (1994)
[Publications] Hope,B.T.: "Induction of a Long-Lasting AP-1 Complex Composed of Altered Fos-like Proteins in Brain by Chronic Cocaine and Other Chronic Treatments" Neuron. 13. 1235-1244 (1994)
[Publications] Furuichi,M.: "Genomic structure and chromosome location of the human mutT homologue gene hMTIXI encoding 8-oxo-dGTPase for prevention of A:T to C:G transversion" Genomics. 24. 485-490 (1994)
[Publications] Oda,S.: "Stabilization of cyclin E and cdk2 mRNAs at G1/S transition in Rat-1A cells emerging from the G0 state" Oncogene. (in press).
[Publications] Oshiro,Y.: "Fibrosarcoma versus fibromatoses and cellular nodular fascitis:A comparative study of their proliferative activity using proliferating cell nuclear antigen,DNA" Am J Surg Pathol. 18. 712-719 (1994)
[Publications] Dorfman,H.D.: "Exophytic variant of fibrous dysplasia (fibrous dysplasiaprotuberans)." HumPathol. 25. 1234-1237 (1994)
[Publications] Oda,Y.: "Case report 877" Skeletal Radiol. 23. 669-671 (1994)
[Publications] Oshiro,Y.: "Atypical fibroxanthoma versus benign and malignant fibrous histiocytoma:A conparative study of their proliferative activity using MIB-I,DNA flow cytometry" Cancer. (in press).
[Publications] Haraguchi,M.: "Angiogenic Enzymes" Nature. 368. 198 (1994)

1994 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] Gunji,T.: "Specific detection of positive and negative stranded hepatitis C viral RNA using chemical RNA modification" Arch.Virol.134. 293-302 (1994)

[Publications] Iizuka,M.: "Mapping of 28(CA)n microsatellite repeats and 13 Alu markers on human chromosome 11 using a panel of somatic cell hybrids" Genomics. 19. 581-584 (1994)

[Publications] Munakata,N.: "Molecular characterization of thirteen gyrA mutations conferring nalidisxic acid resistance in Bacillus subtilis" Mol.Gen.Genet.244. 97-103 (1994)

[Publications] Sachse,R.: "DNA aberrations at the retinoblastoma gene locus in human squamous cell carcinomas of the lung" Oncogene. 9. 39-47 (1994)

[Publications] Yashima,K.: "Mutations of the adenomatous polyposis coli gene in the mutation cluster region:Comparison of human pancreatic and colorectal cancer" Int.J.Cancer. 59. 43-47 (1994)

[Publications] Furihata,C.: "Induction of c-fos and c-myc oncogene in the pyrolic mucosa of rat stomach by N-methyl-N'-nitro-N-nitrosoguanidine and taurocholate" Cancer Letters. 83. 215-220 (1994)

[Publications] Iizuka,M.: "Twelve simple repeat sequence polymorphisms on chromosome 11,4,16 and 21" Hum.Molec.Genet.3. 1707-1708 (1994)

[Publications] Makino,R.: "Cloning and characterization of a c-myc intron binding protein (MIBP1)" Nucleic Acids Res.22. 5679-5685 (1994)

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

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

[Publications] Yasuda,J.: "Cloning and characterization of rat cellular nucleic acid binding protein (CNBP) cDNA" DNA Research,. (in press).

[Publications] Kohno,T.: "Homozygous deletion at chromosome 2q33 in human small-cell lung carcinoma identified by arbitrarily primed PCR genomic finger printing" Oncogene. 9. 103-108 (1994)

[Publications] Levy,E.R.: "DNA rearrangements distal to the Evi-1 locus associated with 3q21q26 syndrome" Blood. 83. 1348-1352 (1994)

[Publications] Suzukawa,K: "Identification of a breakpoint cluster region 3' of the ribophorin I gene at 3q21 associated with the transcriptional activation of the EVI-1 gene in acute" Blood. 84. 2681-2688 (1994)

[Publications] Ohyashiki,K.: "EVI1 expression associated with a 3q26 anomaly in a leukemia cell line derived from the blast crisis of chronic myeloid leukemia" Leukemia. 8. 2169-2173 (1994)

[Publications] Morishita,K.: "EVI-1 zinc finger protein works as a transcriptional activator via binding to a consensus sequence of GACAAGATAAGATAAN1-28 CTCATCTTC." Oncogene. (in press).

[Publications] Nagata,K.: "Solution structure of the epidermal growth factor like domain of helegulin-,a ligand for p180 erbB-4" EMBOJ.13. 3517-3523 (1994)

[Publications] Fusaki,N.: "Characterization of p59fyn-mediated signal transduction on T cell activation" International Immunology. 6. 1245-1255 (1994)

[Publications] Iyama,A.: "A unique structural feature of rabbit DNA repair methyltransferase as revealed by cDNA cloning" Carcinogenesis. 15. 627-663 (1994)

[Publications] Ishibashi,T.: "Artificial control of nuclear translocation of DNA repair methyltransferase" J.Biol.Chem.269. 7645-7650 (1994)

[Publications] Ishibashi,T.: "Intracellular localization and function of DNA repair methyltransferase in human cells" Mutation Res. 315. 199-212 (1994)

[Publications] Hope,B.T.: "Induction of a Long-Lasting AP-1 Complex Composed of Altered Fos-like Proteins in Brain by Chronic Cocaine and Other Chronic Treatments" Neuron. 13. 1235-1244 (1994)

[Publications] Furuichi,M.: "Genomic structure and chromosome location of the human mutT homologue gene hMTIXI encoding 8-oxo-dGTPase for prevention of A:T to C:G transversion" Genomics. 24. 485-490 (1994)

[Publications] Oda,S.: "Stabilization of cyclin E and cdk2 mRNAs at G1/S transition in Rat-1A cells emerging from the G0 state" Oncogene. (in press).

[Publications] Oshiro,Y.: "Fibrosarcoma versus fibromatoses and cellular nodular fascitis:A comparative study of their proliferative activity using proliferating cell nuclear antigen,DNA" Am J Surg Pathol. 18. 712-719 (1994)

[Publications] Dorfman,H.D.: "Exophytic variant of fibrous dysplasia (fibrous dysplasiaprotuberans)." HumPathol. 25. 1234-1237 (1994)

[Publications] Oda,Y.: "Case report 877" Skeletal Radiol. 23. 669-671 (1994)

[Publications] Oshiro,Y.: "Atypical fibroxanthoma versus benign and malignant fibrous histiocytoma:A conparative study of their proliferative activity using MIB-I,DNA flow cytometry" Cancer. (in press).

[Publications] Haraguchi,M.: "Angiogenic Enzymes" Nature. 368. 198 (1994)

林健志九州大学, 遺伝情報実験施設, 教授 (00019671)