Identification and functional analysis of novel stem cell markers in neuronal-related cells

• Project/Area Number: 19790274
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Single-year Grants
• Research Field: Human pathology
• Research Institution: Chiba Cancer Center (Research Institute)
• Principal Investigator: TAKENOBU Hisanori Chiba Cancer Center (Research Institute), 発がん制御研究部, 研究員 (60392247)
• Project Period (FY): 2007 – 2009
• Project Status: Completed (Fiscal Year 2009)
• Budget Amount: ¥3,570,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥570,000); Fiscal Year 2009: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000); Fiscal Year 2008: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2007: ¥1,100,000 (Direct Cost: ¥1,100,000)
• Keywords: 幹細胞 / 発がん / 分化

Research Abstract

We found that CD133 was expressed in several neuroblastoma (NB) cell lines/tumor samples. Intriguingly, CD133 repressed NB cell differentiation, accelerated cell proliferation, anchorage-independent colony formation, and in vivo tumor formation of NB cells. CD133-related differentiation suppression in NB was in part dependent on neurotrophic receptor RET tyrosine kinase regulation. RET transcription was suppressed by CD133 in NB cells and GDNF treatment failed to induce RET in CD133-expressing cells. CD133 in cancer cells and our findings may be applied to improve differentiation induction therapy for NB patients.

Research Products

• [Journal Article] Bmi1 is a MYCN target gene that regulates tumorigenesis through repression of KIF1Bbeta and TSLC1 in neuroblastoma. (2010)
  • Author(s): Ochiai H, Takenobu H, Nakagawa A, Yamaguchi Y, Kimura M, Ohira M, Okimoto Y, Fujimura Y, Koseki H, Kohno Y, Nakagawara A, Kamijo T.
  • Journal Title: Oncogene. 29(18) Pages: 2681-2690
• [Journal Article] Polycomb group molecule PHC3 regulates polycomb complex composition and prognosis of osteosarcoma. (2010)
  • Author(s): Iwata S, Takenobu H, Kageyama H, Koseki H, Ishii T, Nakazawa A, Tatezaki SI, Nakagawara A, Kamijo T.
  • Journal Title: Cancer Sci. (Epub ahead of print)
  • NAID: 10026594687
• [Journal Article] HDM2 impairs Noxa transcription and affects apoptotic cell death in a p53/p73-dependent manner in neuroblastoma. (2010)
  • Author(s): Shi Y, Takenobu H, Kurata K, Yamaguchi Y, Yanagisawa R, Ohira M, Koike K, Nakagawara A, Ling LJ, Kamijo T.
  • Journal Title: Eur. J. Cancer. (in press)
• [Journal Article] Bmil is a MYCN target gene that regulates tumorigenesis through repression of KIF1Bbeta and TSLC1 in neuroblastoma. (2010)
  • Author(s): Ochiai H, Takenobu H, Nakagawa A, Yamaguchi Y, Kimura M, Ohira M, Okimoto Y, Fujimura Y, Koseki H, Kohno Y, Nakagawara A, Kamijo T.
  • Journal Title: Oncogene 29
  • Peer Reviewed
• [Journal Article] Polycomb group molecule PHC3 regulates polycomb complex composition and prognosis of osteosarcoma (2010)
  • Author(s): Iwata S, Takenobu H, Kageyama H, Koseki H, Ishii T, Nakazawa A, Tatezala S, Nakagawara A, Kamijo S.
  • Journal Title: Cancer Science
  • NAID: 10026594687
  • Peer Reviewed
• [Journal Article] Plk1 regulates liver tumor cell death by phosphorylation of TAp63. (2009)
  • Author(s): Komatsu S, Takenobu H, Ozaki T, Ando K, Koida N, Suenaga Y, Ichikawa T, Hishiki T, Chiba T, Iwama A, Yoshida H, Ohnuma N, Nakagawara A, Kamijo T.
  • Journal Title: Oncogene. 28(41) Pages: 3631-3941
• [Journal Article] Plk1 regulates liver tumor cell death by phosphorylation of TAp63. (2009)
  • Author(s): Komatsu S, Takenobu H, Ozaki T, Ando K, Koida N, Suenaga Y, Ichikawa T, Hishiki T, Chiba T, Iwama A, Yoshida H, Ohnuma N, Nakagawara A, Kamijo T.
  • Journal Title: Oncogene 28 Pages: 3631-3641
  • Peer Reviewed
• [Journal Article] N-MYC promotes cell proliferation through a direct transactivation of neuronal leucine-rich repeat protein-1 (NLRR1) gene in neuroblastoma. (2008)
  • Author(s): Hossain MS, Ozaki T, Wang H, Nakagawa A, Takenobu H, Ohira M, Kamijo T, Nakagawara A.
  • Journal Title: Oncogene. 27(46) Pages: 6075-6082
• [Journal Article] N-MYC promotes cell proliferation through a direct transactivation of neuronal leucine-rich repeat protein-1 (NLRR1) gene in neuroblastoma. (2008)
  • Author(s): Hossain MS, Ozaki T, Wang H, Nakagawa A, Takenobu H, Ohira M, Kamiio T, Nakaerawara A.
  • Journal Title: Oncogene 27 Pages: 6075-6082
  • Peer Reviewed
• [Presentation] 幹細胞マーカーCD133はRETの発現抑制を介して神経芽腫の分化を制御する (2010)
  • Author(s): 竹信尚典, 下里修, 大平美紀, 中川原章, 上條岳彦
  • Organizer: 第14回神経芽腫研究会
  • Place of Presentation: 名古屋
• [Presentation] エピジェネティックな制御を受ける幹細胞マーカーCD133はRETの発現制御を介して神経芽腫の分化を制御する (2009)
  • Author(s): 竹信尚典, 下里修, 落合秀匡, 木村昌樹, 山口陽子, 松下せりな, 中島久美子, 中川原章, 上條岳彦
  • Organizer: 第25回白本小児がん学会
  • Place of Presentation: 浦安
  • Year and Date: 2009-11-27
• [Presentation] MYCN target gene CD133 regulates proliferation and sternness of neuroblastoma (2009)
  • Author(s): 竹信尚典, 下里修, 落合秀匡, 木村昌樹, 大平美紀, 中川原章, 上條岳彦
  • Organizer: 第67回日本癌学会学術総会
  • Place of Presentation: 名古屋
• [Presentation] MYCNの新規な標的遺伝子であるCD133は神経芽腫の増殖と幹細胞性を制御する (2009)
  • Author(s): 竹信尚典, 下里修, 落合秀匡, 山口陽子, 松下せりな, 木村昌樹, 大平美紀, 中川原章, 上條岳彦
  • Organizer: 第104回小児血液腫瘍懇話会
  • Place of Presentation: 東京
• [Presentation] CD133 is epigenetically regulated and regulates differentiation via RET in neuroblastoma cells (2009)
  • Author(s): 竹信尚典, 下里修, 落合秀匡, 木村昌樹, 山口陽子, 松下せりな, 中島久美子, 中川原章, 上條岳彦
  • Organizer: 第68回日本癌学会学術総会
  • Place of Presentation: 横浜
• [Presentation] エピジェネティックな制御を受ける幹細胞マーカーCD133はRETの発現制御を介して神経芽腫の分化を制御する (2009)
  • Author(s): 竹信尚典, 下里修, 落合秀匡, 木村昌樹, 山口陽子, 松下せりな, 中島久美子, 中川原章, 上條岳彦
  • Organizer: 第25回日本小児がん学会
  • Place of Presentation: 浦安
• [Presentation] MYCNは幹細胞マーカーCD133の転写を制御する (2008)
  • Author(s): 竹信尚典, 下里修, 落合秀匡, 山口陽子, 松下せりな, 木村昌樹, 大平美紀, 中川原章, 上條岳彦
  • Organizer: 第31回 日本分子生物学会年会, 第81回日本生化学会大会 合同大会
  • Place of Presentation: 神戸
  • Year and Date: 2008-12-10
• [Presentation] MYCN target gene CD133 regulates proliferation and sternness of neuroblastoma (2008)
  • Author(s): 竹信尚典, 下里修, 落合秀匡, 木村昌樹, 大平美紀, 中川原章, 上條岳彦
  • Organizer: 第67回日本癌学会学術総会
  • Place of Presentation: 千葉
  • Year and Date: 2008-11-16
• [Presentation] Stem cell marker CD133 is a novel MYCN target and regulates aggressiveness in neuroblastoma (2008)
  • Author(s): Takenobu H, Shimozato O, Kimura M, Ochiai H, Ohira M, Nakagawara A, Kamijo T
  • Organizer: 2008 国際神経芽腫学会 (ANR 2008)
  • Place of Presentation: 千葉
  • Year and Date: 2008-05-22
• [Presentation] Stem cell marker CD133 is a novel MYCN target and regulates aggressiveness in neuroblastoma (2008)
  • Author(s): 竹信尚典, 下里修, 木村昌樹, 落合秀匡, 大平美紀, 中川原章, 上條岳彦
  • Organizer: 2008国際神経芽腫学会(ANR 2008)
  • Place of Presentation: 千葉
• [Presentation] MYCNの新規転写ターゲットCD133は神経芽腫の増殖と幹細胞性を制御する (2008)
  • Author(s): 竹信尚典, 下里修, 落合秀匡, 木村昌樹, 松下せりな, 山口陽子, 大平美紀, 中川原章, 上條岳彦
  • Organizer: 第24回日本小児がん学会総会
  • Place of Presentation: 千葉
• [Presentation] MYCNは幹細胞マーカーCD133の転写を制御する (2008)
  • Author(s): 竹信尚典, 下里修, 落合秀匡, 山口陽子, 松下せりな, 木村昌樹, 大平美紀, 中川原章, 上條岳彦
  • Organizer: 第31回日本分子生物学会年会, 第81回日本生化学会大会合同大会
  • Place of Presentation: 神戸
• [Presentation] 幹細胞マーカーCD133が神経芽腫のstemnessに及ぼす役割 (2007)
  • Author(s): 竹信尚典, 下里修, 木村昌樹, 大平美紀, 好田忠行, 中川原章, 上條岳彦
  • Organizer: 第23回 日本小児がん学会学術集会
  • Place of Presentation: 仙台
  • Year and Date: 2007-12-16
• [Presentation] Effects of CD133 on stemness-related characters of neuroblastoma cells (2007)
  • Author(s): 竹信尚典, 下里修, 木村昌樹, 中川原章, 上條岳彦
  • Organizer: 第66回 日本癌学会学術総会
  • Place of Presentation: 横浜
  • Year and Date: 2007-10-03
• [Presentation] Effects of CD133 on steMness-related characters of neuroblastoma cells (2007)
  • Author(s): 竹信尚典, 下里修, 木村昌樹, 中川原章, 上條岳彦
  • Organizer: 第66回日本癌学会学術総会
  • Place of Presentation: 横浜
• [Presentation] 幹細胞マーカーCD133が神経芽腫のstemnessに及ぼす役割 (2007)
  • Author(s): 竹信尚典, 下里修, 木村昌樹, 大平美紀, 好田忠行, 中川原章, 上條岳彦
  • Organizer: 第23回日本小児がん学会学術集会
  • Place of Presentation: 仙台
• [Remarks]
  • URL: http://www.chiba-ce.jp/inst/jp/project/011.html
• [Remarks]
  • URL: http://www.chiba-ce.jp/inst/eng/project/011.html