1989 Fiscal Year Annual Research Report

細胞増殖因子作用の分子機構とトランスフォーメーション

Research Project

Project/Area Number	01010060
Research Institution	Keio University
Principal Investigator	清水信義慶応義塾大学, 医学部, 教授 (50162706)
Co-Investigator(Kenkyū-buntansha)	河野通明岐阜薬科大学, 助教授 (00027335) 桑野信彦大分医科大学, 教授 (80037431) 伊藤文昭摂南大学, 薬学部, 教授 (80111764) 西川克三金沢医科大学, 教授 (10029960) 梅田誠横浜市立大学, 木原研, 教授 (70045996)
Keywords	TGF / FGF / EGF / TNF / オートクリン制御 / トランスフォーメーション / チロシン燐酸化 / Cキナーゼ
Research Abstract	梅田はマウス由来のL・P3細胞の培養上清からゼラチン親和性のGCP(還元下で〜270kDa)とヘパリン親和性のGNCP(還元下で〜170kDa)接着因子を精製した。平井(玲)はラットの活性型30kDaTGFはA鎖ホモダイマーPDGFと同一であり、TGF活性はAサブユニットにDNA合成誘起活性はBサブユニットにあることを示唆した。西川はA431細胞のFGFレセプターの分子量は140kおよび170kであることを確認した。春日はGlyーXーGlyーXーXーGlyに関して、変異インスリンレセプターVal^<996>を導入した細胞ではそのレセプター機能を消失することを明らかにした。矢追はV型コラーゲンα_1鎖由来の30K断片が強いインスリン結合性(結合部位はβ鎖)をもち、そのアミノ酸配列はArgに富んでいること、インスリンの保持・安定性を高める働きをしている結果を得た。伊藤はヒト包皮由来FSー4細胞株を用いて、TNF・EGFがアラキドン酸を遊離させることによってプロスタグランジンを産生させ、抑制シグナルとして作用することを示した。桑野はEGF応答欠損変異株(Nー3)が“EGFのオートクリン制御"による新しいトランスフォーメーションの例であることを見出した。河野はシグナル伝達系の中核と考えられる41・43K蛋白のTyr燐酸化に関してこの蛋白質の分離・精製を行った。大竹はラット肝細胞の完全無血清培地での初代培養法を開発し、増殖開始に新しい遺伝子の関与を示唆した。平井(雅)はCキナーゼの主要基質である80K蛋白のアミノ酸配列を決定し、モノクローナル抗体を作製した。天野はKB細胞からのEGF応答欠損変異株を用いてEGFレセプター異常が癌の増殖を抑制する結果を得た。〈若い研究者〉菊池はウシ大脳から低分子量のGTPase活性促進蛋白(GAP)を分離・精製した。竹下はT細胞のILー2レセプターβ鎖が単独でILー2結合能をもち特異的にチロシンリン酸化されて増殖シグナルを伝達することを示した。宮川は癌細胞では分子量130Kの低親和性GMーCSFレセプターが発現されていることを明らかにした。

Research Products

(16 results)

All Other

All Publications (16 results)

[Publications] Ozawa,S.: "Selective Killing of Squamous Carcinoma Cells by Immunotoxin That Recognizes The EGF Receptor." Int.J.Cancer. 43. 152-157 (1989)
[Publications] Amagai,M.: "Cloning of TPA-Inducible Early(TIE)Genes by Differential Hybridization Using a TPA-Nonresponsive Variant of Mouse 3T3-L1 Cells." Somat.Cell Mol.Genet.15. 153-158 (1989)
[Publications] Gamou,S.: "Unique Chromosomal Location of Amplified EGF Receptor genes in the EGF Receptor-Hyperproducing Tumor Cell line NA." Somat.Cell Mol.Genet.15. 179-184 (1989)
[Publications] Hirai,M.: "Lung Cancer Cells Often Express High Level of Protein Kinase C." Jpn.J.Cancer Res.80. 204-208 (1989)
[Publications] Hirai,M: "Stimulation of A Mr 80,000 Protein Phosphorylation by EGF in EGF Receptor-Hyperproducing Human Tumor Cells." J.Cell.Physiol.139. 9-17 (1989)
[Publications] Ozawa,S.: "Prognostic Significance of Epidermal Growth Factor Receptor in Esophageal Squamous Cell Carcinomas." Cancer. 63. 2169-2173 (1989)
[Publications] Shimizu,Y.: "Cell Genetic Evidence of Correlation of Intracellular Translocation of Protein Kinase C(PKC)and the PKC-Mediated Phosphorylation of 80-kDa Protein with Mitogenic Action of Tumor Promoters." Somat.Cell Mol.Genet. 15. 321-329 (1989)
[Publications] Sakai,K.: "Isolation of cDNAs Encoding a Substrate for Protein Kinase C:Nucleotide Sequence and Chromosomal Mapping of the Gene for a Human 80K Protein." Genomics. 5. 309-315 (1989)
[Publications] Gamou,S.: "Subcellular Localization of the EGF Receptor Maturation Process." Exp.Cell Res.183. 197-206 (1989)
[Publications] Kaseda,S.: "Expression of Epidermal Growth Factor Receptors in Four Histologic Cell Types of Lung Cancer." J.Surg.Oncol.42. 16-20 (1989)
[Publications] Yamada,H.: "Reduction of EGF Receptor Levels in Human Tumor Cells Transfected with an Anti-sense RNA Expression Vector." Exp.Cell Res.184. 90-98 (1989)
[Publications] Hirota,N.: "Suppression of an Epidermal Growth Factor Receptor-Hyperproducing Tumor by an Immunotoxin Conjugate of Gelonin and a Monoclonal Anti-Epidermal Growth Factor Receptor Antibody." Cancer Res.49. 7106-7109 (1989)
[Publications] Samuels,D.S.: "Protein Kinase C Phosphorylates DNA Topoisomerase I in vitro." FEBS Litt.259. 57-60 (1989)
[Publications] Kato,M.: "The Pyrimidine/Purine Biased Region of the Epidermal Growth Factor (EGF)Receptor Gene is Sensitive to S1 Nuclease and may Form an Intramolecular Triplex." Biochem.J.251. (1990)
[Publications] Hirai,M.: "Reduced Tyrosine Phosphorylation and Nonrisponsiveness to EGF-Mediated Cytotoxity in EGF a Receptor-Hyperproducing UCVA-1 Cells." Cellular Signalling. 2. (1990)
[Publications] Kikuchi,A.: "Association of EGF Receptor Expression with Proliferating Cells and of ras p21 Expression with Differentiating Cells in Vauious Skin Tumors." Br.J.Dermatol.(1990)

1989 Fiscal Year Annual Research Report

細胞増殖因子作用の分子機構とトランスフォーメーション

Principal Investigator

清水 信義 慶応義塾大学, 医学部, 教授 (50162706)

Research Products

[Publications] Ozawa,S.: "Selective Killing of Squamous Carcinoma Cells by Immunotoxin That Recognizes The EGF Receptor." Int.J.Cancer. 43. 152-157 (1989)

[Publications] Amagai,M.: "Cloning of TPA-Inducible Early(TIE)Genes by Differential Hybridization Using a TPA-Nonresponsive Variant of Mouse 3T3-L1 Cells." Somat.Cell Mol.Genet.15. 153-158 (1989)

[Publications] Gamou,S.: "Unique Chromosomal Location of Amplified EGF Receptor genes in the EGF Receptor-Hyperproducing Tumor Cell line NA." Somat.Cell Mol.Genet.15. 179-184 (1989)

[Publications] Hirai,M.: "Lung Cancer Cells Often Express High Level of Protein Kinase C." Jpn.J.Cancer Res.80. 204-208 (1989)

[Publications] Hirai,M: "Stimulation of A Mr 80,000 Protein Phosphorylation by EGF in EGF Receptor-Hyperproducing Human Tumor Cells." J.Cell.Physiol.139. 9-17 (1989)

[Publications] Ozawa,S.: "Prognostic Significance of Epidermal Growth Factor Receptor in Esophageal Squamous Cell Carcinomas." Cancer. 63. 2169-2173 (1989)

[Publications] Shimizu,Y.: "Cell Genetic Evidence of Correlation of Intracellular Translocation of Protein Kinase C(PKC)and the PKC-Mediated Phosphorylation of 80-kDa Protein with Mitogenic Action of Tumor Promoters." Somat.Cell Mol.Genet. 15. 321-329 (1989)

[Publications] Sakai,K.: "Isolation of cDNAs Encoding a Substrate for Protein Kinase C:Nucleotide Sequence and Chromosomal Mapping of the Gene for a Human 80K Protein." Genomics. 5. 309-315 (1989)

[Publications] Gamou,S.: "Subcellular Localization of the EGF Receptor Maturation Process." Exp.Cell Res.183. 197-206 (1989)

[Publications] Kaseda,S.: "Expression of Epidermal Growth Factor Receptors in Four Histologic Cell Types of Lung Cancer." J.Surg.Oncol.42. 16-20 (1989)

[Publications] Yamada,H.: "Reduction of EGF Receptor Levels in Human Tumor Cells Transfected with an Anti-sense RNA Expression Vector." Exp.Cell Res.184. 90-98 (1989)

[Publications] Hirota,N.: "Suppression of an Epidermal Growth Factor Receptor-Hyperproducing Tumor by an Immunotoxin Conjugate of Gelonin and a Monoclonal Anti-Epidermal Growth Factor Receptor Antibody." Cancer Res.49. 7106-7109 (1989)

[Publications] Samuels,D.S.: "Protein Kinase C Phosphorylates DNA Topoisomerase I in vitro." FEBS Litt.259. 57-60 (1989)

[Publications] Kato,M.: "The Pyrimidine/Purine Biased Region of the Epidermal Growth Factor (EGF)Receptor Gene is Sensitive to S1 Nuclease and may Form an Intramolecular Triplex." Biochem.J.251. (1990)

[Publications] Hirai,M.: "Reduced Tyrosine Phosphorylation and Nonrisponsiveness to EGF-Mediated Cytotoxity in EGF a Receptor-Hyperproducing UCVA-1 Cells." Cellular Signalling. 2. (1990)

[Publications] Kikuchi,A.: "Association of EGF Receptor Expression with Proliferating Cells and of ras p21 Expression with Differentiating Cells in Vauious Skin Tumors." Br.J.Dermatol.(1990)

清水信義慶応義塾大学, 医学部, 教授 (50162706)