1994 Fiscal Year Annual Research Report

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-

Research Project

Project/Area Number	06281113
Research Institution	Hiroshima University
Principal Investigator	田原榮一広島大学, 医学部, 教授 (00033986)
Co-Investigator(Kenkyū-buntansha)	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)
Keywords	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
Research Abstract	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。

Research Products

(34 results)

All Other

All Publications (34 results)

[Publications] 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)
[Publications] 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)
[Publications] 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)
[Publications] 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)
[Publications] Kawaida,K.: "Hepatocyte growth factor prevents acute renal failure and accelerate renal regeneration in mice." Proc.Natl.Acad.Sci.USA. 91. 4357-4361 (1994)
[Publications] 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)
[Publications] 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)
[Publications] 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)
[Publications] 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)
[Publications] 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)
[Publications] 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)
[Publications] Gamou,S.: "Calphostin-c stimulates epidermal growth factor receptor phosphorylation and internalization via light-dependent mechanism." J.Cell Physiol.158. 151-159 (1994)
[Publications] Gamou,S.: "Light-dependent induction of early-response gene expression by calphostin-c." Cell Struct.Funct.19. 195-200 (1994)
[Publications] Gamous,S.: "Hydrogen peroxide preferentially enhances the tyrosine phosphorylation of epidermal growth factor receptor." FEBS Lett.357. 161-164 (1995)
[Publications] 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)
[Publications] 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)
[Publications] 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)
[Publications] Miyasaka,K.: "Frequent loss of heterozygosity on chromosome 4 in diethylnitrosamine-induced C3H/MSM mouse hepatocellular carcinomas in culture." Mol.Carcinogenesis. (in press). (1995)
[Publications] Fukuda,H.: "Helicobacter pylori infection,serum pepsinogen level and gastric cancer." Jpn.J.Cancer Res.86. 64-71 (1995)
[Publications] Katoh,M.: "Cloning and characterization of MST,a novel putative serine/threonine kinase with SH3 domain." Oncogene. 10(in press). (1995)
[Publications] 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)
[Publications] Sasaki,K.: "Estimation of S-phase fraction in tumor tissue sections by immunohistochemical staining of PCNA." J.Histochem.Cytochem.42. 957-960 (1994)
[Publications] 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)
[Publications] Kishi,H.: "Growth regulation of retinal pigment epithelial(RPE) cells in vitro." Curr.Eye.Res.13. 661-668 (1994)
[Publications] Kishi,H.: "Effect of cytokines and prostaglandins on the growth of chick retinal pigment epithelial cells." Curr.Eye Res.13. 833-837 (1994)
[Publications] Segawa,K.: "B cell mitogenic activity of sea squirt antigen." Int.Arch.Aller.and Immunol.104. 270-276 (1994)
[Publications] 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)
[Publications] Asai,A.: "The s-Myc protein having the ability to induce apoptosis is selectively dexpressed in rat embryo chondrocytes." Oncogene. 9. 2345-2352 (1994)
[Publications] Yamamoto,K.: "A reverse transcriptase-polymerase chain reaction detects heterogeous chimeric mRNAs in leukemias with 11q23 abnormalities." Blood. 83. 2912-2921 (1994)
[Publications] 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)
[Publications] Komatsu,H.: "A Variant chromosome translocation at 11q13 identifying PRAD1/Cyclin D1 as the BCL-1 gene." Blood. 84. 1226-1231 (1994)
[Publications] Tahara,E.: "Gann Monograph on Cancer Research" Japan Scientific Societies Press, 178 (1994)
[Publications] 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)
[Publications] Kanda,H.: "Growth Factors:Cell growth,morphogenesis,and transformation" CRC Press, 10 (1994)

1994 Fiscal Year Annual Research Report

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-

Principal Investigator

田原 榮一 広島大学, 医学部, 教授 (00033986)

Research Products

[Publications] 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)

[Publications] 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)

[Publications] 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)

[Publications] 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)

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

[Publications] 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)

[Publications] 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)

[Publications] 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)

[Publications] 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)

[Publications] 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)

[Publications] 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)

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

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

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

[Publications] 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)

[Publications] 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)

[Publications] 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)

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

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

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

[Publications] 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)

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

[Publications] 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)

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

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

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

[Publications] 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)

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

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

[Publications] 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)

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

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

[Publications] 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)

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

田原榮一広島大学, 医学部, 教授 (00033986)