Axin induces cell death and reduces cell proliferation in astrocytoma by activating the p53 pathway.
Axin induces cell death and reduces cell proliferation in astrocytoma by activating the p53 pathway.
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DOI：
10.3892/ijo_00000309
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发表时间：
2009-07
影响因子：
5.2
通讯作者：
Li-ying Zhang;Jingwen Ye;Feng Zhang;Fan-fan Li;Hang Li;Yu-Chen Gu;Fang Liu;Guang-sheng Chen-Guang-sheng-Ch
中科院分区：
文献类型：
--
作者：
Li-ying Zhang;Jingwen Ye;Feng Zhang;Fan-fan Li;Hang Li;Yu-Chen Gu;Fang Liu;Guang-sheng Chen-Guang-sheng-Ch
星形细胞肿瘤是最常见的脑肿瘤，具有各种遗传缺陷。Axin作为一种抑癌基因，可以控制细胞的生长和死亡。Axin具有与p53直接相互作用并调节p53通路活性的单独结构域。我们的目的是阐明Axin在星形细胞瘤进展中的作用。应用免疫组织化学方法检测96例星形细胞瘤中Axin的表达。检测Axin过表达或沉默的C6星形细胞瘤细胞的凋亡指数、增殖活性以及p53及其下游基因p21和Cyclin D1的表达水平。结果显示Axin水平与星形细胞瘤的分级呈负相关（R=-0.286，P<0.05），与Ki-67标记指数呈负相关（R=-0.227，P<0.05）。Axin在C6细胞中过表达可诱导细胞死亡，抑制细胞增殖，上调p53的表达。Axin的沉默降低p53表达。p53抑制剂pifithrin-alpha能够抵消Axin在C6细胞中的作用。我们的数据表明Axin的表达与星形细胞瘤的进展呈负相关。总之，Axin部分通过激活星形细胞瘤细胞中的p53通路诱导细胞死亡并减少细胞增殖。这些知识有助于理解Axin在星形细胞瘤进展中的作用。
Astrocytic tumors are the most common brain tumors with various genetic defects. As a tumor suppressor gene, Axin could control cell death and growth. Axin possesses a separate domain that directly interacts with p53 and regulates the activity of p53 pathway. Our aims were to elucidate the effects of Axin on the progression of astrocytoma. We examined the expression of Axin in 96 cases of astrocytoma using immunohistochemistry. The apoptotic index, proliferactive acitivity and the expression levels of p53 and its downstream genes, p21 and Cyclin D1, were evaluated in the C6 astrocytoma cells with overexpression or silencing of Axin. The results showed the levels of Axin correlated significantly inversely with the grades of astrocytoma (R=-0.286, P<0.05) and correlated negatively with Ki-67 labeling index (R=-0.227, P<0.05). Overexpression of Axin in C6 cells induces cell death, and reduces the cell proliferation, up-regulates the expression of p53. Silencing of Axin reduces p53 expression. The p53 inhibitor, pifithrin-alpha, was able to counteract the effect of Axin in C6 cells. Our data demonstrate that the expression of Axin is associated negatively with the progression of astrocytoma. In conclusion, Axin induces cell death and reduces cell proliferation, partially by activating the p53 pathway in astrocytoma cells. This knowledge is helpful in understanding the role of Axin in the progression of astrocytoma.