1996 年度実績報告書

ヒト消化器がんの増殖制御機構

研究課題

研究課題/領域番号	08265103
研究種目	重点領域研究
研究機関	広島大学
研究代表者	川原榮一広島大学, 医学部, 教授 (00033986)
研究分担者	加藤洋癌研, 病理部, 部長 (20010473) 井藤久雄鳥取大学, 医学部, 教授 (60127610) 広橋説雄国立がんセンター研究所, 副所長 (70129625) 磯村実東京大学, 医科学研究所, 助手 (40272497) 佐々木博己国立がんセンター研究所. 分子腫瘍学部, 室長 (60235265)
キーワード	ヒト消化器がん / インターフェロン / アポトーシス / c-erbB-2 / カドヘリン / カテニン / HGF
研究概要	ヒト消化器がんの増殖制御に深くかかわる分子機構を解析し、以下の諸点を明らかにした. 1.インターフェロンβによる胃がん細胞のアポトーシスは、p27Kip1の誘導と結びつくことが示された。インターフェロン誘導遺伝子6-16は、アンチセンスおよび遺伝子導入実験の研究結果からアポトーシスを制御する機能をもち、更に胃がん細胞の延命に関与することが示唆された。 2.胃がんにおけるアポトーシスは、in vivoおよびin vitroでの解析により、p53遺伝子依存性と非依存性の経路があり、しかもアポトーシス誘発は血球系細胞に比較して明らかに遅延していた。 3.c-erbB-2/EGF受容体とβカテニンのチロシンリン酸化に関する研究から、増殖因子受容体系とカドヘリン細胞接着系との間のシグナル伝達機構は細胞間接着機能のみならず細胞分化(腺管形成)、がん浸潤・転移にも関与する可能性が示唆された。 4.胃がんにおける染色体17q12領域の増幅ユニットの解析から、CAB1,C51,c-erbl32が共通増幅領域に含まれることを明らかにし、またCAB1の遺伝子解析から、StAR遺伝子との類似性があることが示された。 5.HGFアンタゴニスト(HGF/NK4)を精製することに成功し、これはc-mct/HGF受容体に結合し、HGFのmitogen, motogen, morphogen活性を阻害し、更にがん細胞のin vitro浸潤をも抑制した。

研究成果

(22件)

すべてその他

すべて文献書誌 (22件)

[文献書誌] Kuniyasu, H.: "Growth inhibitory effect of interferon-b is associated with the induction of cyclin-dependent kinase inhibitor p27Kip1 in a human gastric carcinoma cell line." Cell Growth & Differentiation. 8. 47-52 (1997)
[文献書誌] Tahara, E: "Molecular biological observations in gastric cancer." Seminars Oncology. 23. 307-315 (1996)
[文献書誌] Kitahara, K.: "Expression of cyclin D1, CDK4 and p27^<KIP1> is associated with the p16^<MTS1> gene status in human esophageal carcinoma cell lines." Journal of Experimental Therapeutics & Oncology. 1. 7-12 (1996)
[文献書誌] Akama, Y.: "No point mutations but a codon 31 polymorphism and decreased expression of the p21^<SDII/WAF1/CIP1/MDA6> gene in human gastric carcinomas." Molecular and Cellular Differentiation. 4. 187-198 (1996)
[文献書誌] Akama, Y.: "Genetic status and expression of the cyclin-dependent kinase inhibitors in human gastric carcinoma cell lines." Jpn. J. Cancer Res.87. 824-830 (1996)
[文献書誌] Yasui, W.: "Expression of cyclin-dependent kinase inhibitor p21^<WAF1/CIP1> in non-neoplastic mucosa and neoplasia of the stomach : Relationship with p53 status and proliferative activity." Journal of Pathology. 180. 122-128 (1996)
[文献書誌] Tatebe, S.: "Apoptosis occurs more frequently in metastatic foci than in primary lesions of human colorectal carcinomas : analysis by terminal-deoxynucleotidyl-transferase-mediated dUTP-biotin nick end labeling." Int. J. Cancer. 65. 173-177 (1996)
[文献書誌] Ohfuji, S.: "Low frequency of apoptosis in epstein-barr virus-associated gastric carcinoma with lymphoid stroma." Int. J. Cancer. 68. 1-7 (1996)
[文献書誌] Ezaki, T.: "Deletion mapping on chromosome 1p in well-diferentiated gastric cancer." British Journal of Cancer. 73. 424-428 (1996)
[文献書誌] Sugimoto, K.: "Molecular cloning and characterization of a newly identified member of the cadherin family, PB-cadherin." The Journal of Biological Chemistry. 271. 11548-11556 (1996)
[文献書誌] Matsumoto, K: "Hepatocyte growth factor in lung morphogenesis and tumor invasion : role as a mediator in epithelium-mesenchyme and tumor-stroma interactions." Cancer Chemother Pharmacol.38. S42-S47 (1996)
[文献書誌] Matsumoto, K.: "Emerging multipotent aspects of hepatocyte growth factor." J. Biochem.119. 591-600 (1996)
[文献書誌] Miura, K.: "Detailed deletion mapping in squamous cell carcinomas of the esophagus narrows a region containing a putative tumor suppressor gene to about 200 kilobases on distal chromosome 9q." Cancer Res.56. 1629-1634 (1996)
[文献書誌] Shibata, T.: "Dominant negative inhibition of the association between b-catenin and c-erbB-2 by N-terminally deleted b-catenin suppresses the invasion and metastasis of cancer cells." Oncogene. 13. 883-889 (1996)
[文献書誌] Inomata, M.: "Alteration of b-catenin expression in colonic epithelial cells of familial adenomatous polyposis patients." Cancer Res.56. 2213-2217 (1996)
[文献書誌] Sakamoto, M.: "Formation of focal adhesion and spreading of polarized human colon cancer cells in association with tyrosine phosphorylation of paxillin in response to phorbol ester." Laboratory Investigation. 74. 199-208 (1996)
[文献書誌] Ono, M.: "Cancer cell morphology at the invasive front and expression of cell adhesion-related carbohydrate in the primary lesion of patients with colorectal carcinoma with liver metastasis." Cancer. 78. 1179-1186 (1996)
[文献書誌] Tsujitani, S.: "Apoptotic cell death and its relationship to carcinogenesis in colorectal carcinoma" Cancer supplement. 77. 1711-1716 (1996)
[文献書誌] Matsumoto, K.: "Acquisition of invasive phenotype in gallbladder cancer cells via mutal interaction of stromal fibroblasts and cancer cells as mediated by hepatocyte growth factor." Jpn. J. Cancer Res.87. 702-710 (1996)
[文献書誌] Koshikawa, N.: "Purification and identification of a novel and four known serine proteinase inhibitors secreted by human glioblastoma cells." J. Biochem.119. 334-339 (1996)
[文献書誌] Miyagi, Y.: "Assignment of the human PP5/TFPI-2 gene to 7q22 by FISH and PCR-based human/rodent cell hybrid mapping panel analysis." Genomics. 35. 267-268 (1996)
[文献書誌] Akaogi, K.: "Specific accumulation of tumor-derived adhesion factor in tumor blood vessels and in capillary tube-like structures of cultured vascular endothelial cells." Proc. Natl. Acad. Sci. USA. 93. 8384-8389 (1996)

1996 年度 実績報告書

ヒト消化器がんの増殖制御機構

研究代表者

川原 榮一 広島大学, 医学部, 教授 (00033986)

研究成果

[文献書誌] Kuniyasu, H.: "Growth inhibitory effect of interferon-b is associated with the induction of cyclin-dependent kinase inhibitor p27Kip1 in a human gastric carcinoma cell line." Cell Growth & Differentiation. 8. 47-52 (1997)

[文献書誌] Tahara, E: "Molecular biological observations in gastric cancer." Seminars Oncology. 23. 307-315 (1996)

[文献書誌] Kitahara, K.: "Expression of cyclin D1, CDK4 and p27^<KIP1> is associated with the p16^<MTS1> gene status in human esophageal carcinoma cell lines." Journal of Experimental Therapeutics & Oncology. 1. 7-12 (1996)

[文献書誌] Akama, Y.: "No point mutations but a codon 31 polymorphism and decreased expression of the p21^<SDII/WAF1/CIP1/MDA6> gene in human gastric carcinomas." Molecular and Cellular Differentiation. 4. 187-198 (1996)

[文献書誌] Akama, Y.: "Genetic status and expression of the cyclin-dependent kinase inhibitors in human gastric carcinoma cell lines." Jpn. J. Cancer Res.87. 824-830 (1996)

[文献書誌] Yasui, W.: "Expression of cyclin-dependent kinase inhibitor p21^<WAF1/CIP1> in non-neoplastic mucosa and neoplasia of the stomach : Relationship with p53 status and proliferative activity." Journal of Pathology. 180. 122-128 (1996)

[文献書誌] Tatebe, S.: "Apoptosis occurs more frequently in metastatic foci than in primary lesions of human colorectal carcinomas : analysis by terminal-deoxynucleotidyl-transferase-mediated dUTP-biotin nick end labeling." Int. J. Cancer. 65. 173-177 (1996)

[文献書誌] Ohfuji, S.: "Low frequency of apoptosis in epstein-barr virus-associated gastric carcinoma with lymphoid stroma." Int. J. Cancer. 68. 1-7 (1996)

[文献書誌] Ezaki, T.: "Deletion mapping on chromosome 1p in well-diferentiated gastric cancer." British Journal of Cancer. 73. 424-428 (1996)

[文献書誌] Sugimoto, K.: "Molecular cloning and characterization of a newly identified member of the cadherin family, PB-cadherin." The Journal of Biological Chemistry. 271. 11548-11556 (1996)

[文献書誌] Matsumoto, K: "Hepatocyte growth factor in lung morphogenesis and tumor invasion : role as a mediator in epithelium-mesenchyme and tumor-stroma interactions." Cancer Chemother Pharmacol.38. S42-S47 (1996)

[文献書誌] Matsumoto, K.: "Emerging multipotent aspects of hepatocyte growth factor." J. Biochem.119. 591-600 (1996)

[文献書誌] Miura, K.: "Detailed deletion mapping in squamous cell carcinomas of the esophagus narrows a region containing a putative tumor suppressor gene to about 200 kilobases on distal chromosome 9q." Cancer Res.56. 1629-1634 (1996)

[文献書誌] Shibata, T.: "Dominant negative inhibition of the association between b-catenin and c-erbB-2 by N-terminally deleted b-catenin suppresses the invasion and metastasis of cancer cells." Oncogene. 13. 883-889 (1996)

[文献書誌] Inomata, M.: "Alteration of b-catenin expression in colonic epithelial cells of familial adenomatous polyposis patients." Cancer Res.56. 2213-2217 (1996)

[文献書誌] Sakamoto, M.: "Formation of focal adhesion and spreading of polarized human colon cancer cells in association with tyrosine phosphorylation of paxillin in response to phorbol ester." Laboratory Investigation. 74. 199-208 (1996)

[文献書誌] Ono, M.: "Cancer cell morphology at the invasive front and expression of cell adhesion-related carbohydrate in the primary lesion of patients with colorectal carcinoma with liver metastasis." Cancer. 78. 1179-1186 (1996)

[文献書誌] Tsujitani, S.: "Apoptotic cell death and its relationship to carcinogenesis in colorectal carcinoma" Cancer supplement. 77. 1711-1716 (1996)

[文献書誌] Matsumoto, K.: "Acquisition of invasive phenotype in gallbladder cancer cells via mutal interaction of stromal fibroblasts and cancer cells as mediated by hepatocyte growth factor." Jpn. J. Cancer Res.87. 702-710 (1996)

[文献書誌] Koshikawa, N.: "Purification and identification of a novel and four known serine proteinase inhibitors secreted by human glioblastoma cells." J. Biochem.119. 334-339 (1996)

[文献書誌] Miyagi, Y.: "Assignment of the human PP5/TFPI-2 gene to 7q22 by FISH and PCR-based human/rodent cell hybrid mapping panel analysis." Genomics. 35. 267-268 (1996)

[文献書誌] Akaogi, K.: "Specific accumulation of tumor-derived adhesion factor in tumor blood vessels and in capillary tube-like structures of cultured vascular endothelial cells." Proc. Natl. Acad. Sci. USA. 93. 8384-8389 (1996)

1996 年度実績報告書

川原榮一広島大学, 医学部, 教授 (00033986)