2001 年度実績報告書

癌の発生・進展においてリボソームの果たす役割の研究

研究課題

研究課題/領域番号	12877030
研究機関	東北大学
研究代表者	堀井明東北大学, 大学院・医学系研究科, 教授 (40249983)
キーワード	リボゾーム / アポトーシス / 乳癌 / 抗S11抗体 / S28 / 14-3-3 / p75NTR / EXTL3 / EXTR1
研究概要	リボゾームはタンパク合成の際に非常に重要な役割を果たしており、そのため、その異常は細胞にとって重大な影響を及ぼすものと考えられる。特に、発がん過程は細胞増殖に異常を来たした結果であり、そこにはリボゾームの関与も考えられる。しかしながら、これまでにこの点を明らかにした研究は行われていない。Fas刺激により、28SのリボゾームRNAが特異的に分解されるが、今回は、リボゾームタンパクの発現の面から検討した。これまでに我々が作成した21種類のヒトリボゾームタンパクを特異的に認識する抗体を用い、乳癌細胞においてFas刺激による影響を検討した結果、21種の抗体のうち、S11抗体がMCF-7細胞において特異的に発現低下を示していた。このS11の発現低下は、これまでの検討では、発現の変化は癌細胞間において不均一に観察されていた。今回観察されたこのS11の発現低下が転写レベルなのか、翻訳レベルなのか、或いはタンパクそのものの安定性や特異的分解によるのかは不明であり、また、発がん過程におけるこの発現低下の意味合いについても未解明である。今後、さらなる検討を加える予定である。また、この他、14-3-3、p75NTR、EXTL3/EXTR1など、種々のアポトーシスに関連する分子についても検討を加えた。本研究の過程において、リボゾームのサブユニットのユビキチンによる分解の過程を効率よく検出する電気泳動システムも開発したので、今後の研究に大いに役立つものと考えられる。

研究成果
(18件)

すべてその他

すべて文献書誌 (18件)

[文献書誌] Semba, S: "Frequent nuclear accumulation of b-catenin (CTNNB1) in human pituitary adenoma"Cancer. 91. 42-48 (2001)
[文献書誌] Sun, C.: "Characterization of the mutations of the K-ras, p53, p16, and SMAD4 genes m 15 human pancreatic cancer cell lines."Oncol, Rep.. 8. 89-92 (2001)
[文献書誌] Sakurada, K.: "RIZ, the retinoblastoma protein interacting zinc finger gene, is mutated in genetically unstable cancers of the pancreas, stomach, and colorectum"Genes Chromosomes Cancer. 30. 207-211 (2001)
[文献書誌] Youssef, E.M.: "Human BAC contig covering the deleted region in pancreatic cancer at 12q21."DNA Seq.. 11. 541-546 (2001)
[文献書誌] Makino, N.: "Isolation and characterization of the human gene homologous to the Drosophila Headcase (hdc) gene in chromosome bands 6q23-q24, a region of common deletion in human pancreatic cancer"DNA Seq.. 11. 547-553 (2001)
[文献書誌] Inoue, H.: "Exclusion of SMAD4 mutation as an early genetic change in human pancreatic ductal adenocarcinoma"Genes Chromosomes Cancer. 31. 295-299 (2001)
[文献書誌] Chen, Y.Z.: "A BAC-based STS-content map spanning a 35-megabase region of human chromosome 1p35-36"Genomics. 74. 55-70 (2001)
[文献書誌] Kaneko, K.: "Analysis of the human pancreatic secretory trypsin inhibitor (PST1) gene mutations in Japanese patients with chronic pancreatitis"J. Hum. Genet.. 46. 293-297 (2001)
[文献書誌] Kondo, E.: "The interacting domains of three MutL heterodimers in man : hMLH1 interacts with 36 homologous amino-acid residues within hMLH3, hPMS1, and hPMS2"Nucl. Acids Res.. 29. 1695-1702 (2001)
[文献書誌] Kato, N.: "Germline mutation of the PTEN gene in a Japanese patient with Cowden's disease"Int. J. Oncol.. 18. 1017-1022 (2001)
[文献書誌] Chen, Y.Z.: "Homozygous deletion in a neuroblastoma cell line defined by a high-density STS map spanning human chromosome band 1p36"Genes Chromosomes Cancer. 31. 326-332 (2001)
[文献書誌] Ishii, S.: "Allelic loss of the NF1 gene in anal malignant melanoma in a patient with neurofibromatosis type 1"Int. J. Clin. Oncol.. 6. 201-204 (2001)
[文献書誌] Nadano D: "Electrophoretic characterization of ribosomal subunits and proteinsin apoptosis specific downregulation of S11 in staurosporine-treated human breast cacinma cells"Bio chem istry. 40. 15184-15193 (2001)
[文献書誌] Kimura M T: "l4-3-3 is involvedin p75 reurotrophin receptor-mediated signal transduction"J Biol Chem.. 276. 17291-17300 (2001)
[文献書誌] Mizuno K: "Overexpression of EXTL3/EXTR1 enhancesNF-kappaB activity induced by TNF-alpha"Cell Signal.. 13. 125-130 (2001)
[文献書誌] Irie S: "Identification of two Fas-associated phosphatase-1 (FAP-1) promotersin human cancercels"DNA Seq.. 11. 519-526 (2001)
[文献書誌] Lefter, L.P.: "Suppression of the tumorigenic phenotype by chromosome 18 transfer into pancreatic cancer cell lines"Genes Chromosomes Cancer. (in press).
[文献書誌] Duda, D.G.: "Overexpression of the p53-inducible brain-specific angiogenesis inhibitor 1 suppresses efficiently tumor angiogenesis"Br. J. Cancer. (in press).

2001 年度 実績報告書

癌の発生・進展においてリボソームの果たす役割の研究

研究代表者

堀井 明 東北大学, 大学院・医学系研究科, 教授 (40249983)

研究成果

[文献書誌] Semba, S: "Frequent nuclear accumulation of b-catenin (CTNNB1) in human pituitary adenoma"Cancer. 91. 42-48 (2001)

[文献書誌] Sun, C.: "Characterization of the mutations of the K-ras, p53, p16, and SMAD4 genes m 15 human pancreatic cancer cell lines."Oncol, Rep.. 8. 89-92 (2001)

[文献書誌] Sakurada, K.: "RIZ, the retinoblastoma protein interacting zinc finger gene, is mutated in genetically unstable cancers of the pancreas, stomach, and colorectum"Genes Chromosomes Cancer. 30. 207-211 (2001)

[文献書誌] Youssef, E.M.: "Human BAC contig covering the deleted region in pancreatic cancer at 12q21."DNA Seq.. 11. 541-546 (2001)

[文献書誌] Makino, N.: "Isolation and characterization of the human gene homologous to the Drosophila Headcase (hdc) gene in chromosome bands 6q23-q24, a region of common deletion in human pancreatic cancer"DNA Seq.. 11. 547-553 (2001)

[文献書誌] Inoue, H.: "Exclusion of SMAD4 mutation as an early genetic change in human pancreatic ductal adenocarcinoma"Genes Chromosomes Cancer. 31. 295-299 (2001)

[文献書誌] Chen, Y.Z.: "A BAC-based STS-content map spanning a 35-megabase region of human chromosome 1p35-36"Genomics. 74. 55-70 (2001)

[文献書誌] Kaneko, K.: "Analysis of the human pancreatic secretory trypsin inhibitor (PST1) gene mutations in Japanese patients with chronic pancreatitis"J. Hum. Genet.. 46. 293-297 (2001)

[文献書誌] Kondo, E.: "The interacting domains of three MutL heterodimers in man : hMLH1 interacts with 36 homologous amino-acid residues within hMLH3, hPMS1, and hPMS2"Nucl. Acids Res.. 29. 1695-1702 (2001)

[文献書誌] Kato, N.: "Germline mutation of the PTEN gene in a Japanese patient with Cowden's disease"Int. J. Oncol.. 18. 1017-1022 (2001)

[文献書誌] Chen, Y.Z.: "Homozygous deletion in a neuroblastoma cell line defined by a high-density STS map spanning human chromosome band 1p36"Genes Chromosomes Cancer. 31. 326-332 (2001)

[文献書誌] Ishii, S.: "Allelic loss of the NF1 gene in anal malignant melanoma in a patient with neurofibromatosis type 1"Int. J. Clin. Oncol.. 6. 201-204 (2001)

[文献書誌] Nadano D: "Electrophoretic characterization of ribosomal subunits and proteinsin apoptosis specific downregulation of S11 in staurosporine-treated human breast cacinma cells"Bio chem istry. 40. 15184-15193 (2001)

[文献書誌] Kimura M T: "l4-3-3 is involvedin p75 reurotrophin receptor-mediated signal transduction"J Biol Chem.. 276. 17291-17300 (2001)

[文献書誌] Mizuno K: "Overexpression of EXTL3/EXTR1 enhancesNF-kappaB activity induced by TNF-alpha"Cell Signal.. 13. 125-130 (2001)

[文献書誌] Irie S: "Identification of two Fas-associated phosphatase-1 (FAP-1) promotersin human cancercels"DNA Seq.. 11. 519-526 (2001)

[文献書誌] Lefter, L.P.: "Suppression of the tumorigenic phenotype by chromosome 18 transfer into pancreatic cancer cell lines"Genes Chromosomes Cancer. (in press).

[文献書誌] Duda, D.G.: "Overexpression of the p53-inducible brain-specific angiogenesis inhibitor 1 suppresses efficiently tumor angiogenesis"Br. J. Cancer. (in press).

2001 年度実績報告書

堀井明東北大学, 大学院・医学系研究科, 教授 (40249983)