REGULATION OF HEMATOPOIETIC CELLS VIA TUMOR SUPPRESSOR GENE WT1

通过肿瘤抑制基因 WT1 调节造血细胞

• 批准号: 07807102
• 负责人: ADACHI Masaki
• 金额: $ 1.15万
• 依托单位: Sapporo Medical University School of Medicine
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 1995
• 资助国家: 日本
• 起止时间: 1995 至 1996
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-07807102/
• 关键词: WT1; Differentiation; G-CSF; wt1腫瘍抑制遺伝子; 細胞分化; 蛋白-蛋白相互作用

The product of the Wilms tumor suppressor gene, WT1, is thought to be a tissue specific transcriptional factor regulating cell growth and differentiation. During cellular differentiation of several hematopoietic, renal and embryonal cells, WT1 expression is downregulated.Considering these data, downregulation of WT1 expression may lead to cellular differentiation. Thus, clarification of regulation of WT1 expression seems to be crucial to control cell differentiation, In this project, we have investigated machinery of regulation of WT1 mRNA expression and tried control WT1 expression levels. The results showed no significant biological effects appeared in several WT1 gene transfectants. We found that G-CSF upregulates the levels of WT1 mRNA expression in human erythroid leukemia K562 cells.However, G-CSF induced neither cellular proliferation nor differentiation of the cells. Thus, we propose that levels of WT1 expression is not directly correlated with cellular differentiation. In order to clarify this proposal, we are investigating whether the observations we found are applied to other cell types.

Wilms肿瘤抑制基因WT 1的产物被认为是调节细胞生长和分化的组织特异性转录因子。在造血细胞、肾细胞和胚胎细胞的分化过程中，WT 1的表达下调，因此，WT 1表达下调可能导致细胞分化。因此，阐明WT 1表达的调控似乎对控制细胞分化至关重要。在本项目中，我们研究了WT 1 mRNA表达的调控机制，并尝试控制WT 1表达水平。结果表明，几个转WT 1基因的植株均未出现明显的生物学效应。我们发现G-CSF可上调人红系白血病K562细胞WT 1 mRNA的表达水平，但G-CSF对K562细胞既无增殖作用，也无分化作用。因此，我们认为WT 1的表达水平与细胞分化没有直接关系。为了澄清这一提议，我们正在研究我们发现的观察结果是否适用于其他细胞类型。

项目成果

Akinori Takaoka: "Anti-cell death activity promotes pulmonary metastasis of melanoma cells" Oncogene. (In press).

Akinori Takaoka：“抗细胞死亡活性促进黑色素瘤细胞的肺转移”Oncogene。

Masaaki Adachi: "Mammalian SH2-containing proteintyrosine phosphatases." Cell. (1996)

Masaaki Adachi：“含有 SH2 的哺乳动物蛋白酪氨酸磷酸酶。”

Satoshi Ugi: "Expression of dominant negative mutant SHPTP2 attenuates phosphatidylinositol 3'-kinase activitv via modultion of phosphorylation of insulin receptor substrate-1." J.Biol. Chem. 271. 12595-12602 (1996)

Satoshi Ugi：“显性失活突变体 SHPTP2 的表达通过调节胰岛素受体底物 1 的磷酸化来减弱磷脂酰肌醇 3-激酶活性。”

Masaaki Adachi: "Predominant expression of the Src homology 2-containing" Virchows Arch. (In press). (1997)

Masaaki Adachi：“包含 Src 同源性 2 的主要表达”Virchows Arch。

Akinori Takaoka: "Anti-cell death activity promotes pulmonary metastasis of melanoma cells" Oncogene. (In press). (1997)

Akinori Takaoka：“抗细胞死亡活性促进黑色素瘤细胞的肺转移”Oncogene。