Survivin and its spliced isoform gene expression is associated with proliferation of renal cancer cells and clinical stage of renal cancer
Survivin and its spliced isoform gene expression is associated with proliferation of renal cancer cells and clinical stage of renal cancer
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DOI：
10.1016/j.canep.2009.06.005
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发表时间：
2009-08-01
影响因子：
2.6
通讯作者：
Suzuki, Kazuhiro
中科院分区：
文献类型：
--
作者：
Okamura, Keigo;Koike, Hidekazu;Suzuki, Kazuhiro
背景：Survivin参与细胞凋亡的抑制。迄今为止，已经描述了选择性剪接的同种型，存活素-2 α，-2B，-Δ Ex 3，-3B。我们评估了生存素基因表达对肾癌细胞增殖的影响，并研究了生存素及其剪接异构体基因表达水平与肾癌临床分期的关系。方法：采用RT-PCR方法检测肾癌细胞Caki-1中Survivin及其剪接体的基因表达。用小分子干扰RNA（siRNA）敲低Survivin基因表达，MTS法检测细胞增殖情况。接下来，我们使用实时定量PCR定量肾切除术样本中生存素及其亚型的基因表达水平。结果：在Caki-1细胞中，Survivin和Survivin-2 α，-2B的表达高于Survivin-Delta Ex 3。转染siRNA后，Survivin基因表达下降，同时细胞增殖也受到抑制，与阴性对照组相比下降了36%（p < 0.01）。在临床肾细胞癌组织中，转移期survivin基因表达水平显著高于远处转移期（M0：M1 = 1：4.81，p = 0.014），pT 3期survivin 213基因表达水平显著高于pT 1期（pT 1：pT 3 = 1：4.50，p = 0.043）。Survivin-2 α表达水平和Survivin-2B/Survivin基因表达水平的比值在各临床分期间均无显著性差异。结论：我们首次证实了肾癌细胞中生存素-2 α的基因表达，并发现生存素及其剪接异构体与肾癌细胞增殖和远处转移有关。(C)2009爱思唯尔有限公司保留所有权利。
Background: Survivin has been implicated in inhibition of apoptosis. To date, alternatively spliced isoforms, Survivin-2 alpha, -2B, -Delta Ex3, -3B, have been described. We assessed the effect of survivin gene expression on the proliferation of renal cancer (RCC) cells, and studied the association of survivin and its spliced isoform gene expression levels with the clinical stage of RCC. Methods: Gene expression of survivin and its spliced isoform in RCC cells, Caki-1, were performed by RT-PCR. We knocked down the gene expression of Survivin using small interfering RNA (siRNA), and assessed the cell proliferation by MTS assay. Next, we quantified the gene expression levels of survivin and its isoform in nephrectomy samples using quantitative real-time PCR. Results: In Caki-1 cells, survivin and survivin-2 alpha, -2B were expressed higher than survivin-Delta Ex3. Decrease of survivin gene expression by transfection of siRNA was accompanied by inhibition of the proliferation of Caki-1 cell with 36% decrease in comparison with negative control transfected cells (p < 0.01). In clinical RCC tissues, survivin expression levels in metastatic stage were significantly higher compared with those in distant metastasis stage (M0:M1 = 1:4.81, p = 0.014); survivin 213 gene expression levels in pT3 tumors were associated significantly higher than those in pT1 (pT1:pT3 = 1:4.50, p = 0.043). No significant differences were found in survivin-2 alpha expression levels and the ratio of survivin-2B/survivin gene expression levels among any clinical stages. Conclusion: We first demonstrated the gene expression of survivin-2 alpha in renal cancer cells, and also showed that survivin and its spliced isoforms had associations with renal cancer cell proliferation and distant metastases. (C) 2009 Elsevier Ltd. All rights reserved.