Wilms tumor suppressor gene WT1 blocks cell cycle progression

Wilms 肿瘤抑制基因 WT1 阻断细胞周期进程

• 批准号: 07457580
• 负责人: AKIYAMA Tetsu
• 金额: $ 1.15万
• 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: 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-07457580/
• 关键词: tumor suppressor gene; Wilms tumor; cell cycle; WT1; Glarrest; apoptosis; leukemia; M1; サイクリン; CDK; 転写因子; 転写制御

We previously demonstrated that overexpression of the Wilms tumor suppressor gene WT1 blocks cell cycle progression from the G1 to S phase. However, we also found that WT1 is highly expressed in human hematopoietic malignancy and there exists a correlation between the levels of WT1 expression and a poor prognosis. Furthermore, suppression of WT1 expression by WT1 anti-sense oligonucleotide inhibits proliferation of leukemia cells. These results suggest that WT1 is important for the proliferation of leukemia cells. To further elucidate the biological significance of WT1 in leukemic cell growth, we overexpressed exogenous WT1 in murine M1 myeloblastic leukemia cells using the IPTG-controlled expression system. We found that induction of WT1 in M1 cells induces G1 arrest and apoptotic cell death. Thus the role of WT1 seems to be different depending on the type of leukemia cell in which it is expressed. We are now trying to isolate cDNAs the expression of which is changed by the action of WT1.

我们以前证明过表达的Wilms肿瘤抑制基因WT 1阻断细胞周期的进展，从G1期到S期。然而，我们也发现WT1在人类造血系统恶性肿瘤中高表达，并且WT1表达水平与不良预后之间存在相关性。此外，通过WT1反义寡核苷酸抑制WT1表达抑制白血病细胞的增殖。这些结果表明，WT1是重要的白血病细胞的增殖。为了进一步阐明WT1在白血病细胞生长中的生物学意义，我们使用IPTG控制的表达系统在小鼠M1成髓细胞白血病细胞中过表达外源性WT1。我们发现，诱导WT 1在M1细胞诱导G1期阻滞和凋亡细胞死亡。因此，WT1的作用似乎取决于其表达的白血病细胞的类型而不同。我们现在正试图分离其表达因WT1的作用而改变的cDNA。

项目成果

Y.Dobashi, T.Kudoh, A.Matsumine, K.Toyoshima & T.Akiyama: "Constitutive overexpression of Cdk2 inhibits neuronal differentiation of rat pheochromocytoma PC12 cells" J.Biol.Chem.270. 23031-23037 (1995)

Y.Dobashi、T.Kudoh、A.Matsumine、K.Toyoshima

T.Kudoh, T.Ishidate, M.Moriyama, K.Toyoshima and T.Akiyama: "G1 phase arrest induced by Wilms tumor protein WT1 is abrogated by cyclin/CDK." Proc.Natl.Acad.Sci.USA. 92. 4517-4521 (1995)

T.Kudoh、T.Ishidate、M.Moriyama、K.Toyoshima 和 T.Akiyama：“Wilms 肿瘤蛋白 WT1 诱导的 G1 期阻滞被细胞周期蛋白/CDK 消除。”

G.-H.Baeg, A.Matsumine, T.Kuroda, R.N.Bhatacharjee, I.Miyashiro, K.Toyoshima & T.Akiyama: "The tumor suppressor gene product APC blocks cell cycle progression from the G0/G1 to S phase" EMBO J.14. 5618-5625 (1995)

G.-H.Baeg、A.Matsumine、T.Kuroda、R.N.Bhatacharjee、I.Miyashiro、K.Toyoshima

G.-H,Baeg,et al.: "The tumor suppressor gene product APC blocks cell cycle progression from the G0/G1 to S phase." EMBOJ. 14. 5618-5625 (1995)

G.-H,Baeg,et al.：“肿瘤抑制基因产物 APC 阻止细胞周期从 G0/G1 期进展到 S 期。”

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