1996 Fiscal Year Annual Research Report

酵母人工染色体を用いた多剤耐性(MDR)遺伝子群の構造と機能に関する共同研究

Research Project

Project/Area Number	06044185
Research Institution	University of Occupational and Environmental Health
Principal Investigator	河野公俊産業医科大学, 医学部, 教授 (00153479)
Co-Investigator(Kenkyū-buntansha)	桑野信彦九州大学, 医学部, 教授 (80037431) 小野眞弓九州大学, 医学部, 講師 (80128347) 和田守正九州大学, 医学部, 助教授 (20220965) COLE Susan P カナダクィーンズ大学, 教授 DEELEY Roger カナダクィーンズ大学, 癌研究所, 所長 FOJO Antonio 米国国立癌研究所, 主任 GREEN Eric D 米国国立衛生研究所, 主任
Keywords	MDR / ヒト7番染色体 / YAC / MRP / ABCトランスポーター / GSX-pump / MOAT / Y-box結合蛋白
Research Abstract	本国際学術研究は平成6年より開始され本年度が最終年度で3年間の共同研究を一応終了することになる。多剤耐性遺伝子(MDR)の中でヒト7番染色体長腕に存在するMDR1及びMDR3を含む領域の人工酵母染色体(YAC)を用いた構造と機能解析については平成7年度に一応の成果をまとめ国際学術誌に2編を発表した。最終年度はさらにこの解析の研究を発展させ、将来の共同研究をにらみ、平成7年度よりカナダのグループを加え、多剤耐性関連遺伝子の中でも中心的な分子として認知されてきたMultidrug resistant associated Gene(MRP)関連の研究をすすめること、さらにMDR1遺伝子の発現制御の分子機序を解析することに主眼をおいて共同研究を進めた。我々はヒトの新しいABCトランスポーターとしてMultispecific organic anion transporter(MOAT)の全長cDNAの分離と塩基配列の決定、遺伝子座の同定に成功した。ヒトMDR1の遺伝子発現は耐性細胞樹立過程において転写活性化をまずひきおこすが、その分子機序は不明であった。そこでMDR1プロモーター領域に結合する転写因子とサウスウェスタン法でクローン化した。その結果転写因子は大腸菌から人までよく保存されたDNA結合領域Cold Shock Domain(CSD)を持つYB-1であることを証明した。本年度は最終年度であり米国国立衛生研究所ゲノムセンター主任のグリーン博士を招聘し、米国のヒトゲノムプロジェクトの最前線の情報に関して、セミナーを開催し意見の交換を行った。さらに本研究を通じてYACの有用性について討議し、その解析法の最終技術についても教授してもらった。以上、本国際学術研究により、この領域の研究が飛躍的に進展できたものと考えている。

Research Products

(13 results)

All Other

All Publications (13 results)

[Publications] Ohga,T.: "Role of the 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)
[Publications] Shono,T.: "Involvement of the transcription factor NF-kB in tubular Morphogenesis of human microvascular endothelial cells by oxidatives stress." Molecular and Cellular Biology. Aug.4231-4239 (1996)
[Publications] Makino,Y.: "Structural and functional analysis of the human Y-box binding protein (YB-1) gene promoter." Nucleic Acids Res.24:10. 1873-1878 (1996)
[Publications] Taniguchi,K.: "Drug-induced down-regulation of topoisomerase I in Human epidermoid cancer cells resistant to saintopin and camptothecins." Cancer Res.56. 2348-2354 (1996)
[Publications] Kawanami,K.: "Decreased DNA topoisomerase IIa expression and cold-sensitive growth in a mouse mammary cancer cell line resistant to etoposide and doxorubicin." Oncology Res.8:5. 197-206 (1996)
[Publications] Fujiwara,S.: "Identification of a 450-kDa human epidermal autoantigen as a new member of the plectin family." The Journal of Investigative Dermatology. 106:5. 1125-1130 (1996)
[Publications] Ono,M.: "Angiogenesis as a new target for cancer treatment." Cancer Chemother Pharmacol. 38. 78-82 (1996)
[Publications] Okimoto,T.: "Regulation of epidermal growth factor receptor by activated H-ras and V-myc oncogenes in mouse balb/3T3 cells : possible roles of AP-1." Oncogene. 12. 1625-1633 (1996)
[Publications] Koike,K.: "Overexpression of multidrug resistance protein gene in human cancer cell lines selected for drug resistance to epipodophyllotoxins." Jpn.J.Cancer Res.87. 765-772 (1996)
[Publications] Taniguchi,K.: "A human canalicular multispecific organic anion transporter (cMOAT) gene is overexpressed in cisplatin-resistant human cancer cell lines with decreased drug accumulation." Cancer Res.56. 4124-4129 (1996)
[Publications] Matsuo,K.: "Human telomeric binding proteins recognizing single and double stranded DNA." International journal of oncology. 9. 1201-1205 (1996)
[Publications] Kawahara,N.: "Enhanced coexpression of thioredoxin and high mobility group protein 1 genes in human hepatocellular carcinoma and the possible association with decreased sensitivity to cisplatin." Cancr Res.56. 5330-5333 (1996)
[Publications] Ryuto,M.: "Induction of vascular endothelial growth factor by tumor necrosis factor a in human glioma cells." The Journal of Biological Chemistry. 271:45. 28220-28228 (1996)

1996 Fiscal Year Annual Research Report

酵母人工染色体を用いた多剤耐性(MDR)遺伝子群の構造と機能に関する共同研究

Principal Investigator

河野 公俊 産業医科大学, 医学部, 教授 (00153479)

Research Products

[Publications] Ohga,T.: "Role of the 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)

[Publications] Shono,T.: "Involvement of the transcription factor NF-kB in tubular Morphogenesis of human microvascular endothelial cells by oxidatives stress." Molecular and Cellular Biology. Aug.4231-4239 (1996)

[Publications] Makino,Y.: "Structural and functional analysis of the human Y-box binding protein (YB-1) gene promoter." Nucleic Acids Res.24:10. 1873-1878 (1996)

[Publications] Taniguchi,K.: "Drug-induced down-regulation of topoisomerase I in Human epidermoid cancer cells resistant to saintopin and camptothecins." Cancer Res.56. 2348-2354 (1996)

[Publications] Kawanami,K.: "Decreased DNA topoisomerase IIa expression and cold-sensitive growth in a mouse mammary cancer cell line resistant to etoposide and doxorubicin." Oncology Res.8:5. 197-206 (1996)

[Publications] Fujiwara,S.: "Identification of a 450-kDa human epidermal autoantigen as a new member of the plectin family." The Journal of Investigative Dermatology. 106:5. 1125-1130 (1996)

[Publications] Ono,M.: "Angiogenesis as a new target for cancer treatment." Cancer Chemother Pharmacol. 38. 78-82 (1996)

[Publications] Okimoto,T.: "Regulation of epidermal growth factor receptor by activated H-ras and V-myc oncogenes in mouse balb/3T3 cells : possible roles of AP-1." Oncogene. 12. 1625-1633 (1996)

[Publications] Koike,K.: "Overexpression of multidrug resistance protein gene in human cancer cell lines selected for drug resistance to epipodophyllotoxins." Jpn.J.Cancer Res.87. 765-772 (1996)

[Publications] Taniguchi,K.: "A human canalicular multispecific organic anion transporter (cMOAT) gene is overexpressed in cisplatin-resistant human cancer cell lines with decreased drug accumulation." Cancer Res.56. 4124-4129 (1996)

[Publications] Matsuo,K.: "Human telomeric binding proteins recognizing single and double stranded DNA." International journal of oncology. 9. 1201-1205 (1996)

[Publications] Kawahara,N.: "Enhanced coexpression of thioredoxin and high mobility group protein 1 genes in human hepatocellular carcinoma and the possible association with decreased sensitivity to cisplatin." Cancr Res.56. 5330-5333 (1996)

[Publications] Ryuto,M.: "Induction of vascular endothelial growth factor by tumor necrosis factor a in human glioma cells." The Journal of Biological Chemistry. 271:45. 28220-28228 (1996)

河野公俊産業医科大学, 医学部, 教授 (00153479)