1998 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)	松本邦夫大阪大学, 医学部, 助教授 (90201780) 加藤洋癌研究所, 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) 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 / 6-16遺伝子 / c-ERBB2遺伝子 / β-カテニン / Tcr / lef / HGF / アポトーシス
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. インターフェロン誘導6-16遺伝子は、老化細胞および胃がん、大腸がんの腫瘍細胞に高発現しているのみならず様々なストレスによっても誘導されること、また6-16蛋白は、CIB(Calcium integrin binding protein)のN端で相互作用することが見い出され、現在6-16とCIBのノックアウトマウスを作成中である。 2. 17q12遺伝子増幅ユニットの両末端部分の連結部位と考えられる複数のDNA断片の同定・クローニングを行った結果、c-ERBB2遺伝子の3'領域を含む12KbのDNA断片中の遺伝子増幅過程での組み換えホットスポットを同定した。また、c-ERBB2の新規エクソンとそのプロモター配列を同定し、その新規エクソンからの転写物は胃癌、食道癌、乳癌などの上皮系癌細胞のみに認められた。 3. 増殖因子受容体からのシグナル伝達がβカテニンのチロシンリン酸化のみならずβカテニンの発現量を増加させ、核内に移行してTcf/lefの転写因子と結合していることを明らかにした。 4. HGFの生物活性を特異的にブロックするHGFアンタゴニスト、HGF/NK4は、腫瘍細胞の増殖、浸潤、転移を阻害し、しかも腫瘍血管内皮細胞の増殖を著しく阻害することを明らかにした。

Research Products

(17 results)

All Other

All Publications (17 results)

[Publications] Nakayama,J.: "Telomerase activation by hTRT in human nomal fibroblasts and hepatocellular carcinomas." Nature Genetics. 18. 65-68 (1998)
[Publications] Kitadai,Y.: "Expression of Interleukin-8 correlates with vascularity in human gastric carcinomas." American Journal of Pathology. 152. 93-100 (1998)
[Publications] Ue,T.: "Co-expression of osteopontin and CD44v9 in gastric cancer." Int.J.Cancer (Pred.Oncol.). 79. 127-132 (1998)
[Publications] Hiyama,T.: "Frequent p53 gene mutations in serrated adenomas of the colorectum." Journal of Pathology. 186. 131-139 (1998)
[Publications] Sasaki,H.: "Presence of streptococcus anginosus DNA in esophageal cancer,dysplasia of esophagus,and gastric cancer." Cancer Res. 58. 2991-2995 (1998)
[Publications] Akiyama,N.: "Presence of multiple,amplifications in esophageal cancer detected by genomic subtraction." Cancer Res.(in press). (1998)
[Publications] Yamane,Y.: "Heterozygosities and allelic frewuencies of 358 dinucleotide-repeat maker loci in the Japanese population." J.Hum Genet. 43. 165-168 (1998)
[Publications] D,Solder B.: "Positional cloning of the gene for Nijimegen breakage syndorome." Nature Genetics. 19. 179-181 (1998)
[Publications] Kanai,Y.: "DNA hypermethylation at the D17S5 locus in associated with gastric carcinogenesis." Cancer Letters. 122. 135-141 (1998)
[Publications] Inomata,M.: "Macroscopic features at the deepest site of tumor penetration presicting liver with melanocyte colonization." Brit.J.Der. 138. 519-521 (1998)
[Publications] Ikeda,M.: "Frequent occurrence of apoptosis is an early event in the oncogenesis of human gastric carcinoma." Virchow Arch. 432. -47 (1998)
[Publications] Tatebe,S.: "Adenovirus transduction efficiency partly correlates with expression levels of integrin α v β 5,but not α v β 3 in human gastric carcinoma cells." Int.J.Mol.Med. 2. 61-64 (1998)
[Publications] Isoshita,N.: "Pathological characteristics of gastric carcinomas in the very old." Jpn.J.Cancer.Res.89. 1-6 (1998)
[Publications] Matsumoto,K.: "Expression of trypsin by epithelial cells of various tissues,leukocytes and neurons in human and mouse." J.Biol.Chem.273. 22913-22920 (1998)
[Publications] Shofuda,K.: "Roke of tissue inhibitor of metalloproteinases-2 (TIMP-2) in regulation of pro-gelatinase A activation catalyzed by membrane-type matrix metalloproteinase-1 (MT1-MMP) in human cancer cells." J.Biochem.124. 462-470 (1998)
[Publications] Koshikawa,N.: "Expression of trypsin by epithelial cells of various tissues,leukocytes and neurons in human and mouse." Amer.J.Pathol.(in press). (1998)
[Publications] Takano,Y.: "Cyclin D2,but not cyclin D1 overexpression correlates with gastric cancer progression and prognosis." Journal of Pathology.(in press). (1998)

1998 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] Nakayama,J.: "Telomerase activation by hTRT in human nomal fibroblasts and hepatocellular carcinomas." Nature Genetics. 18. 65-68 (1998)

[Publications] Kitadai,Y.: "Expression of Interleukin-8 correlates with vascularity in human gastric carcinomas." American Journal of Pathology. 152. 93-100 (1998)

[Publications] Ue,T.: "Co-expression of osteopontin and CD44v9 in gastric cancer." Int.J.Cancer (Pred.Oncol.). 79. 127-132 (1998)

[Publications] Hiyama,T.: "Frequent p53 gene mutations in serrated adenomas of the colorectum." Journal of Pathology. 186. 131-139 (1998)

[Publications] Sasaki,H.: "Presence of streptococcus anginosus DNA in esophageal cancer,dysplasia of esophagus,and gastric cancer." Cancer Res. 58. 2991-2995 (1998)

[Publications] Akiyama,N.: "Presence of multiple,amplifications in esophageal cancer detected by genomic subtraction." Cancer Res.(in press). (1998)

[Publications] Yamane,Y.: "Heterozygosities and allelic frewuencies of 358 dinucleotide-repeat maker loci in the Japanese population." J.Hum Genet. 43. 165-168 (1998)

[Publications] D,Solder B.: "Positional cloning of the gene for Nijimegen breakage syndorome." Nature Genetics. 19. 179-181 (1998)

[Publications] Kanai,Y.: "DNA hypermethylation at the D17S5 locus in associated with gastric carcinogenesis." Cancer Letters. 122. 135-141 (1998)

[Publications] Inomata,M.: "Macroscopic features at the deepest site of tumor penetration presicting liver with melanocyte colonization." Brit.J.Der. 138. 519-521 (1998)

[Publications] Ikeda,M.: "Frequent occurrence of apoptosis is an early event in the oncogenesis of human gastric carcinoma." Virchow Arch. 432. -47 (1998)

[Publications] Tatebe,S.: "Adenovirus transduction efficiency partly correlates with expression levels of integrin α v β 5,but not α v β 3 in human gastric carcinoma cells." Int.J.Mol.Med. 2. 61-64 (1998)

[Publications] Isoshita,N.: "Pathological characteristics of gastric carcinomas in the very old." Jpn.J.Cancer.Res.89. 1-6 (1998)

[Publications] Matsumoto,K.: "Expression of trypsin by epithelial cells of various tissues,leukocytes and neurons in human and mouse." J.Biol.Chem.273. 22913-22920 (1998)

[Publications] Shofuda,K.: "Roke of tissue inhibitor of metalloproteinases-2 (TIMP-2) in regulation of pro-gelatinase A activation catalyzed by membrane-type matrix metalloproteinase-1 (MT1-MMP) in human cancer cells." J.Biochem.124. 462-470 (1998)

[Publications] Koshikawa,N.: "Expression of trypsin by epithelial cells of various tissues,leukocytes and neurons in human and mouse." Amer.J.Pathol.(in press). (1998)

[Publications] Takano,Y.: "Cyclin D2,but not cyclin D1 overexpression correlates with gastric cancer progression and prognosis." Journal of Pathology.(in press). (1998)

田原榮一広島大学, 医学部, 教授 (00033986)