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Internal deletion of BCOR reveals a tumor suppressor function for BCOR in T lymphocyte malignancies
http://hdl.handle.net/10191/50416
http://hdl.handle.net/10191/5041663b4a07f-8ee1-4ed2-bb53-36287ff7f0b0
名前 / ファイル | ライセンス | アクション |
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本文 (59.6 MB)
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要旨 (734.2 kB)
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Item type | 学位論文 / Thesis or Dissertation(1) | |||||
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公開日 | 2018-07-26 | |||||
タイトル | ||||||
タイトル | Internal deletion of BCOR reveals a tumor suppressor function for BCOR in T lymphocyte malignancies | |||||
タイトル | ||||||
言語 | en | |||||
タイトル | Internal deletion of BCOR reveals a tumor suppressor function for BCOR in T lymphocyte malignancies | |||||
言語 | ||||||
言語 | eng | |||||
資源タイプ | ||||||
資源 | http://purl.org/coar/resource_type/c_46ec | |||||
タイプ | thesis | |||||
その他のタイトル | ||||||
その他のタイトル | 内部欠失による変異BCORによりT細胞腫瘍におけるBCORのがん抑制遺伝子としての機能が明らかとなった | |||||
著者 |
Tanaka, Tomoyuki
× Tanaka, Tomoyuki |
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著者別名 | ||||||
識別子 | 51229 | |||||
識別子Scheme | WEKO | |||||
姓名 | 田中, 智之 | |||||
抄録 | ||||||
内容記述タイプ | Abstract | |||||
内容記述 | Recurrent inactivating mutations have been identified in various hematological malignancies in the X-linked BCOR gene encoding BCL6 corepressor (BCOR). However, its tumor suppressor function remains largely uncharacterized. We herein generated mice missing Bcor exon 4, expressing a variant BCOR lacking the BCL6-binding domain. While the deletion of exon 4 in male mice (Bcor^ <ΔE4/y>) compromised the repopulating capacity of hematopoietic stem cells, Bcor^<ΔE4/y> thymocytes had augmented proliferative capacity in culture and showed a strong propensity to induce acute T-cell lymphoblastic leukemia (T-ALL) mostly in a Notch-dependent manner. Myc, one of the critical NOTCH1 targets in T-ALL, was highly upregulated in Bcor^<ΔE4/y> T-ALL cells. ChIP-seq analysis revealed that BCOR was recruited to the Myc promoter and restrained its activation in thymocytes. BCOR also targeted other NOTCH1 targets and potentially antagonized their transcriptional activation. Bcl6-deficient thymocytes behaved in a similar manner to Bcor^<ΔE4/y> thymocytes. Our results provide the first evidence of a tumor suppressor role for BCOR in the pathogenesis of T lymphocyte malignancies. | |||||
内容記述 | ||||||
内容記述タイプ | Other | |||||
内容記述 | 学位の種類: 博士(医学). 報告番号: 甲第4403号. 学位記番号: 新大院博(医)甲第802号. 学位授与年月日: 平成30年3月23日 | |||||
内容記述 | ||||||
内容記述タイプ | Other | |||||
内容記述 | Journal of Experimental Medicine. 2017. 214(10), 2901-2913. | |||||
書誌情報 | p. 1-37, 発行日 2018-03-23 | |||||
出版者 | ||||||
出版者 | 新潟大学 | |||||
DOI | ||||||
識別子タイプ | DOI | |||||
関連識別子 | info:doi/10.1084/jem.20170167 | |||||
著者版フラグ | ||||||
値 | ETD | |||||
学位名 | ||||||
学位名 | 博士(医学) | |||||
学位授与機関 | ||||||
学位授与機関名 | 新潟大学 | |||||
学位授与年月日 | ||||||
学位授与年月日 | 2018-03-23 | |||||
学位授与番号 | ||||||
学位授与番号 | 13101甲第4403号 | |||||
学位記番号 | ||||||
内容記述タイプ | Other | |||||
内容記述 | 新大院博(医)甲第802号 |