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首页> 外文学位 >A study of the effect of an anti-proliferative agent on rat glial tumor cells: Effects on insulin -like growth factor -1 gene expression and action.
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A study of the effect of an anti-proliferative agent on rat glial tumor cells: Effects on insulin -like growth factor -1 gene expression and action.

机译：抗增殖剂对大鼠神经胶质瘤细胞影响的研究：对胰岛素样生长因子-1基因表达和作用的影响。

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摘要

Poly (IC), a synthetic double-stranded RNA co-polymer of inosinic and cytidilic acids, decreases proliferation of normal and tumorigenic cells. I tested the hypothesis that Poly (IC) decreased proliferation of C6 rat glioma cells by disrupting an autocrine IGF-1 growth loop. Poly (IC) decreased the numbers of confluent and sub-confluent C6 cultures. Addition of IGF-1 partially blocked the Poly (IC)-mediated decrease in C6 cell number, suggesting that one mechanism of Poly (IC) action is through down-regulation of IGF-1 gene expression and/or action.;Poly (IC) decreased IGF-1, IGF-1 receptor, IGFBP-4 and IGFBP-5 mRNA levels and decreased immunoreactive IGF-1 peptide, and IGF-1 receptor betaIGFBP-3, IGFBP-4, and IGFBP-5 protein levels in C6 cells. Poly (IC) decreased IGF-1 mRNA independent of new protein synthesis in general and type I interferon (IFN) synthesis in particular. Poly (IC) decreased IGF-1 gene transcription, but did not alter IGF-1 mRNA stability. Poly (IC) activated protein kinase R (PKR) at 5 minutes and increased PKR protein levels at 48 and 72 hours. IGF-1 did not prevent Poly (IC) from activating PKR, but inhibited Poly (IC) from increasing PKR protein levels.;Poly (IC) caused a block in G1 to S transition in confluent C6 cultures whereas in sub-confluent cultures, Poly (IC) decreased the percentage of cells in the G2/M phase. Addition of IGF-1 to Poly (IC)-treated cells decreased the percentage of cells in G0/G1 phase and increased the percentage of cells in G2/M phase in confluent and sub-confluent C6 cultures, indicating reversal of cell cycle blocks. Inhibiting PKR activation also partially prevented the Poly (IC)-mediated cytostasis of C6 cells. Both IGF-1 and a blocking antibody against IFN prevented the increase of PKR levels and the decreased cell proliferation caused by Poly (IC). I conclude that Poly (IC) induces IFN, which mediates the cytostatic effect of Poly (IC) on C6 cells, at least in part through PKR. IGF-1 prevents IFN from inducing PKR, thus explaining the ability of IGF-1 to reverse the cell cycle blocks and the decreased C6 proliferation caused by Poly (IC).
机译：Poly（IC）是肌苷和胞苷酸的合成双链RNA共聚物，可减少正常细胞和致瘤细胞的增殖。我测试了以下假说：聚（IC）通过破坏自分泌的IGF-1生长环来降低C6大鼠神经胶质瘤细胞的增殖。 Poly（IC）减少了融合和次融合C6培养物的数量。加入IGF-1可以部分阻止Poly（IC）介导的C6细胞数量的减少，这表明Poly（IC）作用的一种机制是通过下调IGF-1基因的表达和/或作用。 ）C6细胞中IGF-1，IGF-1受体，IGFBP-4和IGFBP-5 mRNA水平降低，免疫反应性IGF-1肽和IGF-1受体betaIGFBP-3，IGFBP-4和IGFBP-5蛋白水平降低。聚（IC）降低了IGF-1 mRNA的表达，通常与新蛋白的合成无关，特别是I型干扰素（IFN）的合成。聚（IC）降低了IGF-1基因的转录，但没有改变IGF-1 mRNA的稳定性。聚（IC）在5分钟时激活了蛋白激酶R（PKR），并在48和72小时时增加了PKR蛋白水平。 IGF-1不能阻止Poly（IC）激活PKR，但是抑制Poly（IC）增加PKR蛋白水平。; Poly（IC）在融合C6培养物中导致G1向S的转化受阻，而在次融合培养物中，聚（IC）降低了G2 / M期细胞的百分比。将IGF-1添加到经Poly（IC）处理的细胞中可降低融合和亚融合C6培养物中G0 / G1期细胞的百分比，增加G2 / M期细胞的百分比，表明细胞周期阻滞逆转。抑制PKR激活还部分阻止了Poly（IC）介导的C6细胞的细胞停滞。 IGF-1和抗IFN的阻断抗体均可以防止PKR水平的增加和由Poly（IC）引起的细胞增殖的降低。我得出的结论是，Poly（IC）诱导IFN，至少部分通过PKR介导Poly（IC）对C6细胞的抑制细胞作用。 IGF-1阻止IFN诱导PKR，从而解释了IGF-1逆转细胞周期阻滞的能力以及由Poly（IC）引起的C6增殖减少。

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  • 作者

    Chacko, Sapna Mani.;

  • 作者单位

    The University of Texas Health Science Center at San Antonio.;

  • 授予单位 The University of Texas Health Science Center at San Antonio.;
  • 学科 Biochemistry.;Oncology.
  • 学位 Ph.D.
  • 年度 2002
  • 页码 200 p.
  • 总页数 200
  • 原文格式 PDF
  • 正文语种 eng
  • 中图分类
  • 关键词

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