1997 Fiscal Year Annual Research Report

ヒト消化器がんの増殖制御機構

Research Project

Project/Area Number	08265103
Research Institution	Hiroshima University
Principal Investigator	田原榮一広島大学, 医学部, 教授 (00033986)
Co-Investigator(Kenkyū-buntansha)	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) 磯村実癌研, 癌化学療法センターゲノム解析研究部, 研究員 (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)
Keywords	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
Research Abstract	ヒト消化器がんの増殖制御に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.胃がん細胞から分泌されるIL-8は胃がん組織の血管新生を惹起させ、胃がんの増殖・進展に関与することが示唆された。 2.老化細胞およびがん細胞に高発現し、アポトーシスを抑制するインターフェロン誘導6-16について、Yeast two hybrid assayにより6-16とCIB(Calcium integrin binding protein)と結合するクローンが得られ、CIB-MBP融合蛋白と6-16GST融合蛋白とのin vitroでの相互作用が確認された。又、アンチセンスhTR(human telomerase RNA)を、胃がん細胞株MKN-1、TMK-1およびMKN-28に導入すると、前者2株は細胞死に陥るのに対して、MKN-28は、テロメア長の短縮があるのにも拘わらず、6-16高発現の誘導と長期の生存を示した。 3.低分化型胃がんにおいて、K-Sam遺伝子産物とβカテニンのクロストークが存在する可能性が示唆された。 4.食道がんにおける染色体11q13領域の遺伝子増幅ユニットの解析から、cyclin D1が原因遺伝子であり、p16の欠失+cyclin D1遺伝子増幅が食道がんの増殖・進展・転移に関与することが示された。又、染色体11q13、17q12領域の増幅遺伝子のFISHおよび染色体ペインティングによって、遺伝子増幅は増幅ユニット上の遺伝子群が連なって他の染色体に移って起こる可能性が示された。 5.HGFの様々な生物活性をブロックするHGFアンタゴニスト(HGF/NK4)は、胆のうがんの増殖・浸潤を抑制するのにならず強力な腫瘍血管新生阻止能を有することが、in vitro、in vivoで明らかにされた。

Research Products

(12 results)

All Other

All Publications (12 results)

[Publications] Matsumoto, K.: "Acquisition of invasive phenotype in gallbladder cancer cells via mutual interaction of stromal fibroblasts and cancer cells as mediated by hepatocyte growth factor." Jpn.J.Cancer Res.87. 702-710 (1996)
[Publications] Naka, K.: "Growth inhibition of cultitured human gastric cancer cells by 9-cis-retinoic acid with induction of cdk inhibitor Waf1/Cip1/Sdi1/p21 protein." Differentiation. 61. 313-320 (1997)
[Publications] Kuniyasu, H.: "Expression of human telomerase RNA is an early event of stomach carcinogenesis." Jpn.J.Cancer Res.88. 103-107 (1997)
[Publications] Yasui, W.: "Recuced expression of cyclin-dependent kinase inhibitor p27Kip1 is associated with advanced stage and invasiveness of gastric carcinomas." Jpn.J.Cancer Res.88. 625-629 (1997)
[Publications] Kuniyasu, H.: "Growth inhibitory effect of interferon-β is associated with the induction of cyclin-dependent kinase inhibitor p27^<Kip1> in a human gastric carcinoma cell line." Cell Growth & Differentiation. 8. 47-52 (1997)
[Publications] Nagashima, Y.: "Expression of matrilysin in vascular endothelial cells adjacent to matrilysin-producing tumors." Int.J.Cancer. 72. 441-445 (1997)
[Publications] Kishi, T.: "Molecular cloning of human GRB-7co-amplified with CAB1 and c-ERBB-2 in primary gastric cancer." Biochem.Biophys.Res.Commun.232. 5-9 (1997)
[Publications] Akiyama, N.: "Isolation of a candidate gene,CAB1,for cholesterol transport to mitchondoria from an amplicon containing c-ERBB-2 by a modified cDNA selection method." Cancer Res. 57. 3548-3553 (1997)
[Publications] Inomata, M.: "Alteration of β-catenin expression in colonic epithelial cells of familial ademoatous polyposis patients." Cancer Res.56. 2213-2217 (1997)
[Publications] Hayashi, H.: "Expression of fas antigen and its mediation of apoptosis in human gastric cancer cell lines." Jpn.J.Cancer Res.88. 49-55 (1997)
[Publications] Osaki, M.: "5-Fluorouracil (5FU) induced apoptosis in gastric cancer cell lines : tole of the p53" Apoptosi.2. 221-226 (1997)
[Publications] Ouyang, H.: "The insulin-like growth factor II receptor gene is mutated in genetically unstable cancers of the endometrium, stomach, and colorectum." Cancer Res.57. 1851-1854 (1997)

1997 Fiscal Year Annual Research Report

ヒト消化器がんの増殖制御機構

Principal Investigator

田原 榮一 広島大学, 医学部, 教授 (00033986)

Research Products

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

[Publications] Naka, K.: "Growth inhibition of cultitured human gastric cancer cells by 9-cis-retinoic acid with induction of cdk inhibitor Waf1/Cip1/Sdi1/p21 protein." Differentiation. 61. 313-320 (1997)

[Publications] Kuniyasu, H.: "Expression of human telomerase RNA is an early event of stomach carcinogenesis." Jpn.J.Cancer Res.88. 103-107 (1997)

[Publications] Yasui, W.: "Recuced expression of cyclin-dependent kinase inhibitor p27Kip1 is associated with advanced stage and invasiveness of gastric carcinomas." Jpn.J.Cancer Res.88. 625-629 (1997)

[Publications] Kuniyasu, H.: "Growth inhibitory effect of interferon-β is associated with the induction of cyclin-dependent kinase inhibitor p27^<Kip1> in a human gastric carcinoma cell line." Cell Growth & Differentiation. 8. 47-52 (1997)

[Publications] Nagashima, Y.: "Expression of matrilysin in vascular endothelial cells adjacent to matrilysin-producing tumors." Int.J.Cancer. 72. 441-445 (1997)

[Publications] Kishi, T.: "Molecular cloning of human GRB-7co-amplified with CAB1 and c-ERBB-2 in primary gastric cancer." Biochem.Biophys.Res.Commun.232. 5-9 (1997)

[Publications] Akiyama, N.: "Isolation of a candidate gene,CAB1,for cholesterol transport to mitchondoria from an amplicon containing c-ERBB-2 by a modified cDNA selection method." Cancer Res. 57. 3548-3553 (1997)

[Publications] Inomata, M.: "Alteration of β-catenin expression in colonic epithelial cells of familial ademoatous polyposis patients." Cancer Res.56. 2213-2217 (1997)

[Publications] Hayashi, H.: "Expression of fas antigen and its mediation of apoptosis in human gastric cancer cell lines." Jpn.J.Cancer Res.88. 49-55 (1997)

[Publications] Osaki, M.: "5-Fluorouracil (5FU) induced apoptosis in gastric cancer cell lines : tole of the p53" Apoptosi.2. 221-226 (1997)

[Publications] Ouyang, H.: "The insulin-like growth factor II receptor gene is mutated in genetically unstable cancers of the endometrium, stomach, and colorectum." Cancer Res.57. 1851-1854 (1997)

田原榮一広島大学, 医学部, 教授 (00033986)