1994 年度実績報告書

細胞増殖因子からみた癌細胞と間質細胞との相互作用 -その分子機構-

研究課題

研究課題/領域番号	06281113
研究機関	広島大学
研究代表者	田原榮一広島大学, 医学部, 教授 (00033986)
研究分担者	井出利憲広島大学, 医学部, 教授 (60012746) 清水信義慶応義塾大学, 医学部, 教授 (50162706) 河野通明岐阜薬科大学, 薬学部, 助教授 (00027335) 松本邦夫大阪大学, 医学部, 助手 (90201780) 駒田雅之関西医科大学, 医学部, 助手 (10225568)
キーワード	増殖因子 / 増殖因子レセプター / 癌と間質との相互作用 / シグナル伝達 / HGF / c-met / p115
研究概要	HGFは正常組織では主に間質細胞によって産生・分泌されるが、種々のヒト悪性腫瘍(グリオーマ、肺小細胞癌、胃癌、大腸癌、食道癌など)ではHGF転写の多様性オートクリンループが存在し、癌細胞の遊走・浸潤促進に重要な役割を演ずることが示された。HGFのtwo-kringle variantに加えて、本年度ではHGF light chainのみをコードする新しいHGF異常転写産物が胃癌培養株HSC-39で発現していることが見いだされ、現在その機能について解析中である。またHGF誘導因子として、IL-1-alpha,IL-1-betaのみならず、PDGF,FGF(aFGF,bFGF)などの増殖因子も含まれることが明らかにされ、これらサイトカインと増殖因子がHGF/c-met系を介しての癌細胞-間質細胞相互作用を惹起させ、癌の悪性化に関与する可能性が示唆された。そして、本年度最も興味ある点は、HGF,EGF,PDGFなどの増殖因子によってチロシン・リン酸化されるp115の構造が明らかにされ、p115は増殖因子のシグナル伝達に普遍的な、そしてユニークな役割を果たす因子であることが示唆された。

研究成果
(34件)

すべてその他

すべて文献書誌 (34件)

[文献書誌] Tannapfel,A.: "Effect of hepatocyte growth factor on the expression of E- and P-cadherin in gastric carcinoma cell lines." Virchows Archiv. 425. 139-144 (1994)
[文献書誌] Friess,H.: "Cripto,a member of the epidermal growth factor family,is over-expressed in human pancreatic cancer and chronic pancreatitis." Int.J.Cancer. 56. 668-674 (1994)
[文献書誌] Komada,M.: "Regulatory role of major tyrosine autophosphorylation site of kinase domain of c-Met receptor(scatter factor/hepatocyte growth factor receptor)." J.Biol.Chem.269. 16131-16136 (1994)
[文献書誌] Itakura,Y.: "Autocrine stimulation of motility in SBC-5 human lung carcinoma cells by a two-kringle variant of HGF." Cancer Lett.83. 235-243 (1994)
[文献書誌] Kawaida,K.: "Hepatocyte growth factor prevents acute renal failure and accelerate renal regeneration in mice." Proc.Natl.Acad.Sci.USA. 91. 4357-4361 (1994)
[文献書誌] Matsumoto,K.: "Hepatocyte growth factor/scatter scator induces tyrosine phosphrylation of focal adhesion kinase (p125FAK) and promotes migration and invasion by oral squamous cell carcinoma cells." J.Biol.Chem.269. 31807-31813 (1994)
[文献書誌] Nakayama,Y.: "Enhanced invasive activity and decreased expression of tissue inhibitors of metalloproteinases by hepatocyte growth factor in human renal cancer cells." Cancer J.6. 213-219 (1993)
[文献書誌] Morimoto,A.: "Cooperative roles of hepatocyte growth factor and plasminogen activator in tubular morphogenesis by human microvascullar endothelial cells." Jpn.J.Cancer.Res.85. 53-62 (1994)
[文献書誌] Izumi,H.: "Cross talk of tumor necrosis factor-alpha and epidermal growth factor in human microvascular endothelial cells." Expt.Cell Res.214. 654-662 (1994)
[文献書誌] Nakashima,S.: "Tyrosine phosphorylation and activation of mitogen-activated proteinkinases by thrombin in human platelets:Possible involvement in late arachidonic acid release." Biochem.Biophys.Res.Commun.198. 497-503 (1994)
[文献書誌] Hattori,A.: "Tumor necrosis factor is markedly synergistic with interleukin 1 and interferon-gammma in stimulating the prodution of nerve growth factor in fibroblasts." FEBS Lett.340. 177-180 (1994)
[文献書誌] Gamou,S.: "Calphostin-c stimulates epidermal growth factor receptor phosphorylation and internalization via light-dependent mechanism." J.Cell Physiol.158. 151-159 (1994)
[文献書誌] Gamou,S.: "Light-dependent induction of early-response gene expression by calphostin-c." Cell Struct.Funct.19. 195-200 (1994)
[文献書誌] Gamous,S.: "Hydrogen peroxide preferentially enhances the tyrosine phosphorylation of epidermal growth factor receptor." FEBS Lett.357. 161-164 (1995)
[文献書誌] Tahara,H.: "Increase in expression level of p21 sdil/cipl/wafl with increasing division age in both normal and SV40-transformed human fibroblasts." Oncogene. 9(in press). (1995)
[文献書誌] Hukami,J.: "Transforming growth factor-beta has both promoting and inhibiting effects on induction of DNA synthesis in human fibroblasts." Exp.Cell.Res.216. 107-112 (1995)
[文献書誌] Hara,E.: "Id-related genes encoding helix-loop-hellix proteins are required for G1 progression and are repressed in senescent human fibroblasts." J.Biol.Chem.269. 2139-2145 (1994)
[文献書誌] Miyasaka,K.: "Frequent loss of heterozygosity on chromosome 4 in diethylnitrosamine-induced C3H/MSM mouse hepatocellular carcinomas in culture." Mol.Carcinogenesis. (in press). (1995)
[文献書誌] Fukuda,H.: "Helicobacter pylori infection,serum pepsinogen level and gastric cancer." Jpn.J.Cancer Res.86. 64-71 (1995)
[文献書誌] Katoh,M.: "Cloning and characterization of MST,a novel putative serine/threonine kinase with SH3 domain." Oncogene. 10(in press). (1995)
[文献書誌] Sasaki,K.: "Flow cytometric analysis of the expression of PCNA during the cell cycle in HeLa cells and effects of the inhibition of DNA synthesis on it." Cytometry. 14. 876-882 (1993)
[文献書誌] Sasaki,K.: "Estimation of S-phase fraction in tumor tissue sections by immunohistochemical staining of PCNA." J.Histochem.Cytochem.42. 957-960 (1994)
[文献書誌] Beppu,T.: "Identification of S-phase cells with PC10 antibody to proliferating cell nuclear antigen by flow cytometric analysis." J.Histochem.Cytochem.42. 1177-1182 (1994)
[文献書誌] Kishi,H.: "Growth regulation of retinal pigment epithelial(RPE) cells in vitro." Curr.Eye.Res.13. 661-668 (1994)
[文献書誌] Kishi,H.: "Effect of cytokines and prostaglandins on the growth of chick retinal pigment epithelial cells." Curr.Eye Res.13. 833-837 (1994)
[文献書誌] Segawa,K.: "B cell mitogenic activity of sea squirt antigen." Int.Arch.Aller.and Immunol.104. 270-276 (1994)
[文献書誌] Asai,A.: "Negative effects of wild-type p53 and s-Myc on cellular growth and tumorigenicity of glioma cells." J.Neuro-Oncol.19. 259-268 (1994)
[文献書誌] Asai,A.: "The s-Myc protein having the ability to induce apoptosis is selectively dexpressed in rat embryo chondrocytes." Oncogene. 9. 2345-2352 (1994)
[文献書誌] Yamamoto,K.: "A reverse transcriptase-polymerase chain reaction detects heterogeous chimeric mRNAs in leukemias with 11q23 abnormalities." Blood. 83. 2912-2921 (1994)
[文献書誌] Goto,H.: "Acute myelomonocytic leukemia after treatment with chronic oral etoposide:Are MLL and LTG9 genes targets for etoposide?" Int.J.Hematol.60. 145-149 (1994)
[文献書誌] Komatsu,H.: "A Variant chromosome translocation at 11q13 identifying PRAD1/Cyclin D1 as the BCL-1 gene." Blood. 84. 1226-1231 (1994)
[文献書誌] Tahara,E.: "Gann Monograph on Cancer Research" Japan Scientific Societies Press, 178 (1994)
[文献書誌] Tahara,E.: "Proceedings of the 24th International Symposium of the Princess Takamatsu Cancer Research Fund" Princeton Scientific Publishing Co.,Inc.,Princeton,New Jersey,USA, 357 (1994)
[文献書誌] Kanda,H.: "Growth Factors:Cell growth,morphogenesis,and transformation" CRC Press, 10 (1994)

1994 年度 実績報告書

細胞増殖因子からみた癌細胞と間質細胞との相互作用 -その分子機構-

研究代表者

田原 榮一 広島大学, 医学部, 教授 (00033986)

研究成果

[文献書誌] Tannapfel,A.: "Effect of hepatocyte growth factor on the expression of E- and P-cadherin in gastric carcinoma cell lines." Virchows Archiv. 425. 139-144 (1994)

[文献書誌] Friess,H.: "Cripto,a member of the epidermal growth factor family,is over-expressed in human pancreatic cancer and chronic pancreatitis." Int.J.Cancer. 56. 668-674 (1994)

[文献書誌] Komada,M.: "Regulatory role of major tyrosine autophosphorylation site of kinase domain of c-Met receptor(scatter factor/hepatocyte growth factor receptor)." J.Biol.Chem.269. 16131-16136 (1994)

[文献書誌] Itakura,Y.: "Autocrine stimulation of motility in SBC-5 human lung carcinoma cells by a two-kringle variant of HGF." Cancer Lett.83. 235-243 (1994)

[文献書誌] Kawaida,K.: "Hepatocyte growth factor prevents acute renal failure and accelerate renal regeneration in mice." Proc.Natl.Acad.Sci.USA. 91. 4357-4361 (1994)

[文献書誌] Matsumoto,K.: "Hepatocyte growth factor/scatter scator induces tyrosine phosphrylation of focal adhesion kinase (p125FAK) and promotes migration and invasion by oral squamous cell carcinoma cells." J.Biol.Chem.269. 31807-31813 (1994)

[文献書誌] Nakayama,Y.: "Enhanced invasive activity and decreased expression of tissue inhibitors of metalloproteinases by hepatocyte growth factor in human renal cancer cells." Cancer J.6. 213-219 (1993)

[文献書誌] Morimoto,A.: "Cooperative roles of hepatocyte growth factor and plasminogen activator in tubular morphogenesis by human microvascullar endothelial cells." Jpn.J.Cancer.Res.85. 53-62 (1994)

[文献書誌] Izumi,H.: "Cross talk of tumor necrosis factor-alpha and epidermal growth factor in human microvascular endothelial cells." Expt.Cell Res.214. 654-662 (1994)

[文献書誌] Nakashima,S.: "Tyrosine phosphorylation and activation of mitogen-activated proteinkinases by thrombin in human platelets:Possible involvement in late arachidonic acid release." Biochem.Biophys.Res.Commun.198. 497-503 (1994)

[文献書誌] Hattori,A.: "Tumor necrosis factor is markedly synergistic with interleukin 1 and interferon-gammma in stimulating the prodution of nerve growth factor in fibroblasts." FEBS Lett.340. 177-180 (1994)

[文献書誌] Gamou,S.: "Calphostin-c stimulates epidermal growth factor receptor phosphorylation and internalization via light-dependent mechanism." J.Cell Physiol.158. 151-159 (1994)

[文献書誌] Gamou,S.: "Light-dependent induction of early-response gene expression by calphostin-c." Cell Struct.Funct.19. 195-200 (1994)

[文献書誌] Gamous,S.: "Hydrogen peroxide preferentially enhances the tyrosine phosphorylation of epidermal growth factor receptor." FEBS Lett.357. 161-164 (1995)

[文献書誌] Tahara,H.: "Increase in expression level of p21 sdil/cipl/wafl with increasing division age in both normal and SV40-transformed human fibroblasts." Oncogene. 9(in press). (1995)

[文献書誌] Hukami,J.: "Transforming growth factor-beta has both promoting and inhibiting effects on induction of DNA synthesis in human fibroblasts." Exp.Cell.Res.216. 107-112 (1995)

[文献書誌] Hara,E.: "Id-related genes encoding helix-loop-hellix proteins are required for G1 progression and are repressed in senescent human fibroblasts." J.Biol.Chem.269. 2139-2145 (1994)

[文献書誌] Miyasaka,K.: "Frequent loss of heterozygosity on chromosome 4 in diethylnitrosamine-induced C3H/MSM mouse hepatocellular carcinomas in culture." Mol.Carcinogenesis. (in press). (1995)

[文献書誌] Fukuda,H.: "Helicobacter pylori infection,serum pepsinogen level and gastric cancer." Jpn.J.Cancer Res.86. 64-71 (1995)

[文献書誌] Katoh,M.: "Cloning and characterization of MST,a novel putative serine/threonine kinase with SH3 domain." Oncogene. 10(in press). (1995)

[文献書誌] Sasaki,K.: "Flow cytometric analysis of the expression of PCNA during the cell cycle in HeLa cells and effects of the inhibition of DNA synthesis on it." Cytometry. 14. 876-882 (1993)

[文献書誌] Sasaki,K.: "Estimation of S-phase fraction in tumor tissue sections by immunohistochemical staining of PCNA." J.Histochem.Cytochem.42. 957-960 (1994)

[文献書誌] Beppu,T.: "Identification of S-phase cells with PC10 antibody to proliferating cell nuclear antigen by flow cytometric analysis." J.Histochem.Cytochem.42. 1177-1182 (1994)

[文献書誌] Kishi,H.: "Growth regulation of retinal pigment epithelial(RPE) cells in vitro." Curr.Eye.Res.13. 661-668 (1994)

[文献書誌] Kishi,H.: "Effect of cytokines and prostaglandins on the growth of chick retinal pigment epithelial cells." Curr.Eye Res.13. 833-837 (1994)

[文献書誌] Segawa,K.: "B cell mitogenic activity of sea squirt antigen." Int.Arch.Aller.and Immunol.104. 270-276 (1994)

[文献書誌] Asai,A.: "Negative effects of wild-type p53 and s-Myc on cellular growth and tumorigenicity of glioma cells." J.Neuro-Oncol.19. 259-268 (1994)

[文献書誌] Asai,A.: "The s-Myc protein having the ability to induce apoptosis is selectively dexpressed in rat embryo chondrocytes." Oncogene. 9. 2345-2352 (1994)

[文献書誌] Yamamoto,K.: "A reverse transcriptase-polymerase chain reaction detects heterogeous chimeric mRNAs in leukemias with 11q23 abnormalities." Blood. 83. 2912-2921 (1994)

[文献書誌] Goto,H.: "Acute myelomonocytic leukemia after treatment with chronic oral etoposide:Are MLL and LTG9 genes targets for etoposide?" Int.J.Hematol.60. 145-149 (1994)

[文献書誌] Komatsu,H.: "A Variant chromosome translocation at 11q13 identifying PRAD1/Cyclin D1 as the BCL-1 gene." Blood. 84. 1226-1231 (1994)

[文献書誌] Tahara,E.: "Gann Monograph on Cancer Research" Japan Scientific Societies Press, 178 (1994)

[文献書誌] Tahara,E.: "Proceedings of the 24th International Symposium of the Princess Takamatsu Cancer Research Fund" Princeton Scientific Publishing Co.,Inc.,Princeton,New Jersey,USA, 357 (1994)

[文献書誌] Kanda,H.: "Growth Factors:Cell growth,morphogenesis,and transformation" CRC Press, 10 (1994)

1994 年度実績報告書

田原榮一広島大学, 医学部, 教授 (00033986)