Analysis of the mechanisms involved in the cell cycle arrest at G2-M phases and possible clinical utility in the field of ginecology.

分析 G2-M 期细胞周期停滞的机制以及在妇科领域可能的临床应用。

基本信息

  • 批准号:
    15591789
  • 负责人:
  • 金额:
    $ 2.3万
  • 依托单位:
  • 依托单位国家:
    日本
  • 项目类别:
    Grant-in-Aid for Scientific Research (C)
  • 财政年份:
    2003
  • 资助国家:
    日本
  • 起止时间:
    2003 至 2004
  • 项目状态:
    已结题

项目摘要

We observed elongation of cell cycle and accumulation of cells with anomalies in cell division when CaSki human cervical cancer cells were cultured at temperatures lower than usual 37℃. An impaired cell cycle progression at M phase is a possible cause of abnormal chromosome segregation, aneuploidy, cell growth inhibition, and cell death. To investigate the mechanisms involved in these anomalies in cell division, we analyzed changes in gene expression in the cells after the cultivation temperature shift from 37℃ to 32℃ or 30℃, by using a cDNA microarray technique, RT-PCR and western blotting. The results showed that, among those factors related to stress response, ATF2 mRNA was reduced to 60% and 38%, respectively, of the original revel 6 hrs and 12 hrs after the temperature shift. ATF3 expression also was reduced to 75% and 49%, respectively, 6 hrs and 12 hrs after the temperature shift. Expression of both CHOP (C/EBP-homologous protein) and CREB (cAMP responsive element-binding protein)1 gene was suppressed by approximately 40% in 6 to 12 hrs. mRNA of p21^<GP1>, a Cdk inhibitor modulating cell cycle, started to decrease 12 hrs after the temperature shift, and kept repressed until 24 hrs to 72 hrs after the temperature shift. On the contrary, p57^<kip2> expression increased 1.8 fold in 48 hrs. Expression of p53 doubled in 6 hrs, returned to the original revel at 24 hrs, and fallen to 50% at 72 hrs. Expression of MAD2, a factor related to spindle check point, was up regulated 3 fold in 24 hrs in parallel with an increase of M phase cells. Although STK15 (Aurora A) expression declined to 27% 12 hrs after the temperature shift, it elevated to 170% 48 hrs after the temperature change. STK12 expression steadily raised 1.5 fold within 72 hrs after the temperature shift.
我们观察到CaSki人宫颈癌细胞在低于正常温度(37 ℃)下培养时,细胞周期延长,细胞聚集,细胞分裂异常。M期细胞周期进程受损可能是染色体分离异常、非整倍性、细胞生长抑制和细胞死亡的原因。为了探讨这些异常细胞分裂的机制,我们分析了基因表达的变化后,培养温度从37 ℃到32 ℃或30 ℃,通过使用cDNA微阵列技术,RT-PCR和蛋白质印迹。结果表明,在与应激反应相关的因子中,温度变化后6 h和12 h,ATF2 mRNA水平分别下降到原来水平的60%和38%。在温度转换后6小时和12小时,ATF3表达也分别降低至75%和49%。CHOP(C/EBP同源蛋白)和CREB(cAMP反应元件结合蛋白)1基因的表达在6至12小时内被抑制约40%。Cdk抑制剂p21 α mRNA在温度变化后12小时开始下降,并持续抑制至温度变化后24 - 72小时。<GP1>相反,在48小时内,p57 α表达增加1.8倍。<kip2>p53表达在6小时内增加一倍,24小时恢复到原来的水平,72小时下降到50%。与纺锤体检查点相关的因子MAD2的表达在24小时内上调3倍,与M期细胞的增加平行。虽然STK15(Aurora A)表达在温度变化后12小时下降至27%,但在温度变化后48小时升高至170%。STK12表达在温度转换后72小时内稳定地增加1.5倍。

项目成果

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MORINAGA Tomonori其他文献

MORINAGA Tomonori的其他文献

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{{ truncateString('MORINAGA Tomonori', 18)}}的其他基金

Translational regulation of aurora-A kinase expression and its implication for the progression of gynecological cancers.
极光 A 激酶表达的翻译调控及其对妇科癌症进展的影响。
  • 批准号:
    17591766
  • 财政年份:
    2005
  • 资助金额:
    $ 2.3万
  • 项目类别:
    Grant-in-Aid for Scientific Research (C)

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  • 批准号:
    18590188
  • 财政年份:
    2006
  • 资助金额:
    $ 2.3万
  • 项目类别:
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