神経芽腫の増殖・分化・細胞死を抑制する新規NLRR受容体ファミリーの解析と応用

2011 年度 研究成果報告書

• 研究課題/領域番号: 21390317
• 研究種目: 基盤研究(B)
• 配分区分: 補助金
• 応募区分: 一般
• 研究分野: 小児科学
• 研究機関: 千葉県がんセンター(研究所)
• 研究代表者: 中川原 章 千葉県がんセンター(研究所), 研究局, センター長 (50117181)
• 研究分担者: 高取 敦志 千葉県がんセンター(研究所), 研究局, 研究員 (40455390)
• 連携研究者: 中村 洋子 千葉県がんセンター(研究所), 研究局, 主席研究員 (60260254)
• 研究期間 (年度): 2009 – 2011
• キーワード: NLLRR1 / NLRR2 / NLRR3 / Neuroblastoma / 細胞増殖

研究概要

神経芽腫cDNAプロジェクトから同定した新規遺伝子NLRRfamilyの機能解析を行った。その結果、NLRR1は細胞増殖を促進してがんの進展に寄与することが明らかになり、作製したノックアウトマウスの解析によりlipidraftを介した細胞増殖シグナルを増強することが明らかになった。また、NLRR1を標的にした治療用単クローン抗体を作製に成功した。一方、NLRR2はERストレスを誘導し、細胞の生存シグナルを負に制御した。NLRR3は逆に細胞の分化を誘導し、MYCNにより負に転写制御されていた。以上の結果から、NLRRfamilyは神経芽腫における増殖、分化、細胞死の制御をファミリー間で役割分担していることが明らかになった。

研究成果

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• [雑誌論文] CREB represses p53-dependent transactivation of MDM2 through the complex formation with p53 and contributes to p53-mediated apoptosis in response to glucose deprivation (2011)
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• [雑誌論文] The benchmark analysis of gastric, colorectal and rectal cancer pathways : toward establishing standardized clinical pathway in the cancer care (2011)
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  • 査読あり
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• [雑誌論文] Polycomb group molecule PHC3 regulates polycomb complex composition and prognosis of osteosarcoma (2010)
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  • DOI: DOI:10.1084/jem.20082299
  • 査読あり
• [雑誌論文] International consensus for neuroblastoma molecular diagnostics : Report from the international neuroblastoma risk group(INRG) biology committee (2009)
  • 著者名/発表者名: Ambros PF, Ambros IM, Brodeur GM, Haber M, Khan J, Nakagawara A, Schleiermacher G, Speleman F, Spitz R, London WB, Cohn SL, Pearson ADJ, Maris JM
  • 雑誌名: Br. J. Cancer 巻: 100 ページ: 1471-1482
  • DOI: DOI:10.1038/sj.bjc.6605014
  • 査読あり
• [雑誌論文] Distinct role of ShcC docking protein in the differentiation of neuroblastoma (2009)
  • 著者名/発表者名: Miyake I, Ohira M, Nakagawara A, Sakai R
  • 雑誌名: Oncogene 巻: 28 ページ: 662-673
  • DOI: DOI:10.1038/onc.2008.413
  • 査読あり
• [雑誌論文] High expression of ncRAN, a novel non-coding RNA mapped to chromosome 17q25.1, is associated with poor prognosis in neuroblastoma (2009)
  • 著者名/発表者名: Yu M, Ohira M, Li Y, Niizuma H, Oo ML, Zhu Y, Ozaki T, Isogai E, Nakamura Y, Koda T, Oba S, Yu B, Nakagawara A
  • 雑誌名: Int. J. Oncol 巻: 34 ページ: 931-938
  • DOI: DOI:10.3892/ijo_00000219
  • 査読あり
• [雑誌論文] Clinicopathological relevance of UbcH10 in breast cancer (2009)
  • 著者名/発表者名: Fujita T, Ikeda H, Kawasaki K, Taira N, Ogasawara Y, Nakagawara A, Doihara H
  • 雑誌名: Cancer Sci 巻: 100 ページ: 238-248