1995 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	07273104
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, 講師 (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 / インターフェロン / アポトーシス / 癌と間質との相互作用 / HGF / シグナル伝達 / Hrs
研究概要	繊維芽細胞から分泌されるインターフェロン(IFNβ)を介しての癌細胞と繊維芽細胞との相互作用について胃癌細胞株を用いて解析した結果、TMK-1を除く他の胃癌細胞株はIFNβ抵抗性であり、TMK-1細胞株のみに増殖抑制とアポトーシスが認められた。その機序については、IFNβによるp27^<Kip1>の誘導、次いでCDK2キナーゼの低下と高いリン酸化型Rb蛋白の減少が関与していることが示された。そして、TMK-1細胞では、IFNβによるStat91と6-16の誘導がみられ、更に6-16過剰発現TMT-1細胞ではIFNβによるアポトーシスは全く認められなかった。一方、胃癌組織の78%は、正常胃粘膜上皮に比べて6-16過剰発現を示している。従って、IFNβを介した胃癌・間質相互作用が存在するものと考えられた。次に、癌細胞(肺癌、胃癌、胆のう癌、メラノーマ、グリオーマ)と間質細胞の間にはHGFならびにその誘導因子(IL-1, bFGF, PDGF)をメディエータとするループされた相互作用が存在し、HGFによる癌細胞の運動能の亢進には細胞間接着あるいは細胞-マトリス接着蛋白のリン酸化とMAPキナーゼの活性化が重要である可能性が示唆された。そして、HGFを含む多くの増殖因子によってチロシン・リン酸化される分子量115kDaの蛋白、Hrsは早期エンドソームに局在し、増殖因子によって惹起される極初期の現象に関与していると考えられた。

研究成果
(19件)

すべてその他

すべて文献書誌 (19件)

[文献書誌] Tahara, E.: "Molecular biology of gastric cancer." World. J. Surg.19. 484-490 (1995)
[文献書誌] Kitadai, Y.: "Multiparametric in situ messenger RNA hybridization analysis to detect metastasis-related genes in surgical specimens of human colon carcinomas." Clin. Cancer Res.1. 1095-1102 (1995)
[文献書誌] Kitadai, Y.: "In situ mRNA hybridization technique for analysis of metastasis-related genes in human colon carcinoma cells." American Journal of Pathology. 147. 1238-1247 (1995)
[文献書誌] Kitahara, K.: "Expression of cyclin D1, CDK4 and p27KIP1 is associated with the p16MTS1 gene status in human esophageal carcinoma cell lines." Journal of Experimental Therapeutics & Oncology. 1. 7-12 (1996)
[文献書誌] Komada, M.: "Growth factor-induced tyosine phosphorylation of Hrs, a novel 115-kilodalton protein with a structurally conserved putative zinc finger domain." Mol. Cell. Biol.15. 6213-6221 (1995)
[文献書誌] Matsumoto, K.: "Novel function of prostaglandins as inducer of gene expression of hepatocyte growth factor." J. Biochem.117. 458-464 (1995)
[文献書誌] Matsumoto, K.: "Hepatocyte growth factor as a potent survival factor for rat pheochromocytoma PC12 cells." Exp. Cell Res.220. 71-78 (1995)
[文献書誌] Samoto, K.: "Expression of vascular endothelial growth factor and its possible relation with neovascularization in human brain tumors." Cancer Res.55. 1189-1193 (1995)
[文献書誌] Oka, H.: "Constitutive activation of mitogen-activated protein(MAP)kinase in human renal cell carcinoma." Cancer Res.55. 4182-4187 (1995)
[文献書誌] Gamou, S.: "Hydrogen Peroxide preferentially enhances the tyrosine phosphorylation of epidermal growth factor receptor." FEBS Lett.375. 161-164 (1995)
[文献書誌] Tahara, H.: "Increase in experssion level of p21 sdi1/cip1/waf1 with increasing division age in both normal and SV40-transformed human fibroblasts." Oncogene. 10. 835-840 (1995)
[文献書誌] Tahara, H.: "Increase in experssion levels of interferon-inducible genes in senescent human diploid fibroblasts and in SV40-transformed human fibroblasts with extended lifespan." Oncogene. 11. 1125-1132 (1995)
[文献書誌] Miyasaka, K.: "Frequent loss of heterozygosity on chromosome-4 in diethyl nitrosamine-induced C3H/MSM mouse hepatocellular carcinomas in culture." Molecular Carcinogenesis. 13. 37-43 (1995)
[文献書誌] Katoah, M.: "Cloning and characterization of MST, a novel putative serine/threonine kinase with SH3 domain." Oncogene. 10. 1447-1451 (1995)
[文献書誌] Katoh, M.: "Bone metastasis from colorectal cancer in autopsy cases." Journal of Gastroenterology. 30. 615-618 (1995)
[文献書誌] Sasaki, K.: "Monosomy of chromosome 18 detected by FISH in colorectal tumous." Cancer. 76. 1132-1138 (1995)
[文献書誌] Inokuchi, N.: "Stimulatory effect of interleukin-1α on proliferation through a Ca2+/calmodulin-dependent pathway of a human thyroid carcinoma cell line, NIM1." Jpn. J. Cancer Res.86. 670-676 (1995)
[文献書誌] Miyagi, Y.: "Elevated levels of eukaryotic translation initiation factor eIF-4E, mRNA in a broad spectrum of transformed cell lines." Cancer Letters. 91. 247-252 (1995)
[文献書誌] Miyagi, Y.: "Abundant expression of translation factor EIF-4E in post-meiotic germ cells of the rat testis." Laboratory Investigation. 73. 890-898 (1995)

1995 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] Tahara, E.: "Molecular biology of gastric cancer." World. J. Surg.19. 484-490 (1995)

[文献書誌] Kitadai, Y.: "Multiparametric in situ messenger RNA hybridization analysis to detect metastasis-related genes in surgical specimens of human colon carcinomas." Clin. Cancer Res.1. 1095-1102 (1995)

[文献書誌] Kitadai, Y.: "In situ mRNA hybridization technique for analysis of metastasis-related genes in human colon carcinoma cells." American Journal of Pathology. 147. 1238-1247 (1995)

[文献書誌] Kitahara, K.: "Expression of cyclin D1, CDK4 and p27KIP1 is associated with the p16MTS1 gene status in human esophageal carcinoma cell lines." Journal of Experimental Therapeutics & Oncology. 1. 7-12 (1996)

[文献書誌] Komada, M.: "Growth factor-induced tyosine phosphorylation of Hrs, a novel 115-kilodalton protein with a structurally conserved putative zinc finger domain." Mol. Cell. Biol.15. 6213-6221 (1995)

[文献書誌] Matsumoto, K.: "Novel function of prostaglandins as inducer of gene expression of hepatocyte growth factor." J. Biochem.117. 458-464 (1995)

[文献書誌] Matsumoto, K.: "Hepatocyte growth factor as a potent survival factor for rat pheochromocytoma PC12 cells." Exp. Cell Res.220. 71-78 (1995)

[文献書誌] Samoto, K.: "Expression of vascular endothelial growth factor and its possible relation with neovascularization in human brain tumors." Cancer Res.55. 1189-1193 (1995)

[文献書誌] Oka, H.: "Constitutive activation of mitogen-activated protein(MAP)kinase in human renal cell carcinoma." Cancer Res.55. 4182-4187 (1995)

[文献書誌] Gamou, S.: "Hydrogen Peroxide preferentially enhances the tyrosine phosphorylation of epidermal growth factor receptor." FEBS Lett.375. 161-164 (1995)

[文献書誌] Tahara, H.: "Increase in experssion level of p21 sdi1/cip1/waf1 with increasing division age in both normal and SV40-transformed human fibroblasts." Oncogene. 10. 835-840 (1995)

[文献書誌] Tahara, H.: "Increase in experssion levels of interferon-inducible genes in senescent human diploid fibroblasts and in SV40-transformed human fibroblasts with extended lifespan." Oncogene. 11. 1125-1132 (1995)

[文献書誌] Miyasaka, K.: "Frequent loss of heterozygosity on chromosome-4 in diethyl nitrosamine-induced C3H/MSM mouse hepatocellular carcinomas in culture." Molecular Carcinogenesis. 13. 37-43 (1995)

[文献書誌] Katoah, M.: "Cloning and characterization of MST, a novel putative serine/threonine kinase with SH3 domain." Oncogene. 10. 1447-1451 (1995)

[文献書誌] Katoh, M.: "Bone metastasis from colorectal cancer in autopsy cases." Journal of Gastroenterology. 30. 615-618 (1995)

[文献書誌] Sasaki, K.: "Monosomy of chromosome 18 detected by FISH in colorectal tumous." Cancer. 76. 1132-1138 (1995)

[文献書誌] Inokuchi, N.: "Stimulatory effect of interleukin-1α on proliferation through a Ca2+/calmodulin-dependent pathway of a human thyroid carcinoma cell line, NIM1." Jpn. J. Cancer Res.86. 670-676 (1995)

[文献書誌] Miyagi, Y.: "Elevated levels of eukaryotic translation initiation factor eIF-4E, mRNA in a broad spectrum of transformed cell lines." Cancer Letters. 91. 247-252 (1995)

[文献書誌] Miyagi, Y.: "Abundant expression of translation factor EIF-4E in post-meiotic germ cells of the rat testis." Laboratory Investigation. 73. 890-898 (1995)

1995 年度実績報告書

田原榮一広島大学, 医学部, 教授 (00033986)