Functional analyses of the new tumor suppressor candidate gene in hematological malignancies

新抑癌候选基因在血液系统恶性肿瘤中的功能分析

• 批准号: 18591043
• 负责人: HANGAISHI Akira
• 金额: $ 2.57万
• 依托单位: The University of Tokyo
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2006
• 资助国家: 日本
• 起止时间: 2006 至 2007
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-18591043/
• 关键词: tumor suppressor; Blimp-1; cell cycle; 造血器腫瘍

B lymphocyte-induced maturation protein-1 (Blimp-1) is a transcriptional repressor and is reported to be required for differentiation of many cell lineages. We have previously found that Blimp-1 is located within a common region homozygously deleted in lymphoid malignancies and is mutated in primary lymphoid tumors, suggesting that Blimp-1 has a tumor suppressor role. Here we focus on investigating the effect of Blimp-1 on cell cycle regulation. Exogenous expression of Blimp-1 rapidly induces the expression of p53, p57 and p21, and the cells are arrested at G1/G0 and G2/M phases. Further investigations showed that Blimp-1 induced G1/G0 arrest is dependent on wild type pRb while its effect on G2/M arrest requires functional p53, and as the upstream regulators of pRb, p57 and p21 evoked by Blimp-1 play the cooperative roles on keeping active pRb. A Blimp-1 mutation detected in malignant lymphoma was also found to lose its function in cell cycle arrest. These results suggest that Blimp-1 plays an important role in cell cycle control and therefore the suppression of tumor formation.

B淋巴细胞诱导成熟蛋白-1 （Blimp-1）是一种转录抑制因子，据报道是许多细胞系分化所必需的。我们之前发现，Blimp-1位于淋巴细胞恶性肿瘤中纯合缺失的共同区域内，并在原发性淋巴细胞肿瘤中发生突变，这表明Blimp-1具有肿瘤抑制作用。本文主要研究Blimp-1对细胞周期调控的影响。外源表达Blimp-1可快速诱导p53、p57和p21的表达，细胞停留在G1/G0和G2/M期。进一步研究表明，Blimp-1诱导的G1/G0阻滞依赖于野生型pRb，而其对G2/M阻滞的作用需要p53的功能，并且作为pRb的上游调控因子，Blimp-1诱发的p57和p21在保持pRb活性方面发挥协同作用。在恶性淋巴瘤中检测到的Blimp-1突变也被发现在细胞周期阻滞中失去功能。这些结果表明，Blimp-1在细胞周期控制中起重要作用，从而抑制肿瘤的形成。

项目成果

Genomewide screening of DNA copy number changes in chronic myelogenous leukemia with the use of high-resolution array-based comparative genomic hybridization

• DOI: 10.1002/gcc.20303
• 发表时间: 2006-05-01
• 期刊: GENES CHROMOSOMES & CANCER
• 影响因子: 3.7
• 作者: Hosoya, N;Sanada, M;Ogawa, S
• 通讯作者: Ogawa, S

6q欠失の標的癌抑制遺伝子Blimp-1の細胞周期制御における機能解析

6q缺失靶抑癌基因Blimp-1在细胞周期调控中的功能分析

• 发表时间: 2007
• 作者: 王 莉莉;半下石 明など
• 通讯作者: 半下石 明など

Functional analyses of Blimp-1, a tumorsuppersor gene in 6q, in cell cycle

6q肿瘤上基因Blimp-1在细胞周期中的功能分析

• 发表时间: 2007
• 作者: Wang Lili;Akira Hangaishi;et. al.
• 通讯作者: et. al.

Unbalanced translocation der(1 ; 7)(g10 ; p10) defines a unique clinicopathological subgroup of myeloid neoplasms

不平衡易位 der(1 ; 7)(g10 ; p10) 定义了骨髓肿瘤的独特临床病理学亚组

• 发表时间: 2007
• 期刊: Leukemia 21(5)
• 作者: Sanada M;Uike N;Ohyashiki K;Ozawa K;Lili W;Hangaishi A;Kanda Y;Chiba S;Kurokawa M;Omine M;Mitani K;Ogawa S.
• 通讯作者: Ogawa S.

Highly sensitive method for genomewide detection of allelic composition in nonpaired, primary tumor specimens by use of affymetrix single-nucleotide-polymorphism genotyping microarrays

• DOI: 10.1086/518809
• 发表时间: 2007-07-01
• 期刊: AMERICAN JOURNAL OF HUMAN GENETICS
• 影响因子: 9.8
• 作者: Yamamoto, Go;Nannya, Yasuhito;Ogawa, Seishi
• 通讯作者: Ogawa, Seishi