The role of the tumor suppressor gene WT1 in human leukemogenesis.

肿瘤抑制基因 WT1 在人类白血病发生中的作用。

• 批准号: 11470210
• 负责人: SUGIYAMA Haruo
• 金额: $ 9.28万
• 依托单位: Osaka University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (B).
• 财政年份: 1999
• 资助国家: 日本
• 起止时间: 1999 至 2000
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-11470210/
• 关键词: leukemia; The WT1 gene; apoptosis; WT1; tumor suppressor gene; oncogene; WWドメイン

1. The wild-type WT1 gene was expressed in not only leukemia but also solid tumors, including lung cancers. The growth of these cancer cells was inhibited by the treatment with WT1 antisense oligomers.2. Leukemic cell line K562 was arrested at G_2/M checkpoint by the treatment with WT1 antisense oligomers.3. We have established the method to measure individually four different splicing variants (17AA+/KTS+, 17AA+/KTS-, 17AA-/KTS+, 17AA-/KTS-). By using this method, it was found that a 17AA+/KTS+ transcript was major in leukemic cells.4. When the wild-type WT1 gene was transfected into myeloid progenitor cell 32D and the gene was constitutively expressed, the apoptosis of the 32D cells was inhibited.5. A novel WT1-binding protein was cloned and named as WTIP was localized in splicesome and so considered as a splicing factor.

1.野生型WT 1基因不仅在白血病中表达，而且在包括肺癌在内的实体瘤中表达。WT 1反义寡聚体处理后，肿瘤细胞的生长受到抑制.用WT 1反义寡聚体处理白血病细胞株K562，使其阻滞于G_2/M期.我们建立了分别检测17 AA +/KTS+、17 AA +/KTS-、17 AA-/KTS+、17 AA-/KTS-四种不同剪接变体的方法。通过使用这种方法，发现白血病细胞中主要是17 AA +/KTS+转录本。4.将野生型WT 1基因转染髓系祖细胞32 D，使其组成型表达，可抑制32 D细胞的凋亡.克隆了一个新的WT 1结合蛋白，命名为WTIP，该蛋白定位于剪接体中，被认为是一种剪接因子。

项目成果

Harada,Y. et al.: "The WT1 expression in human testicular germ cell tumors."Mol.Urol. 3. 357-363 (1999)

原田，Y.

Tsuboi A.et al.: "Constitutive expression of the Wilms' tumor gene WT1 inhibits the differentiation of myeloid progenitor cells but promotes then proliferation in response to granulocyte-colony stimulating factor(G-CSF)"Leukemia Research. 23. 499-505 (199

Tsuboi A.等人：“肾母细胞瘤基因 WT1 的组成型表达抑制骨髓祖细胞的分化，但响应粒细胞集落刺激因子 (G-CSF) 促进增殖”白血病研究。

Inoue K.et al.: "Wilms' tumor gone (WT1)competes with differentiation-inducing signal in hematopoietic progenitor cells"Blood. 91. 2969-2976 (1998)

Inoue K.等人：“肾母细胞瘤消失（WT1）与造血祖细胞中的分化诱导信号竞争”血液。

Tsuboi, A.et al.: "Constitutive expression of the Wilms' tumor gene WT1 inhibits the differentiation of myeloid progenitor cells but promotes their proliferation in response to granulocyte-colony stimulating factor (G-CSF)."Leuk.Res.. 23. 499-505 (1999)

Tsuboi, A. 等人：“维尔姆斯肿瘤基因 WT1 的组成型表达会抑制骨髓祖细胞的分化，但会促进粒细胞集落刺激因子 (G-CSF) 的增殖。”Leuk.Res.. 23

Oji Y. et al: "Expression of the Wilms' tumor gene WT1 in solid tumors and its involvement in tumor cell growth"Japanese Journal of Cancer Research. 90. 194-204 (1999)

Oji Y.等人：“维尔姆斯肿瘤基因WT1在实体瘤中的表达及其参与肿瘤细胞生长”日本癌症研究杂志。