The Karyopherin proteins, Crm1 and Karyopherin beta1, are overexpressed in cervical cancer and are critical for cancer cell survival and proliferation.
The Karyopherin proteins, Crm1 and Karyopherin beta1, are overexpressed in cervical cancer and are critical for cancer cell survival and proliferation.
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DOI：
10.1002/ijc.24146
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发表时间：
2009-04-15
影响因子：
6.4
通讯作者：
Leaner VD
中科院分区：
文献类型：
--
作者：
van der Watt PJ;Maske CP;Hendricks DT;Parker MI;Denny L;Govender D;Birrer MJ;Leaner VD
Karyopherin蛋白参与核质运输，并且对于蛋白质和RNA亚细胞定位至关重要。最近的研究表明，它们在核膜组件组装，有丝分裂和复制中很重要。由于这些都是关键的细胞功能，核转运蛋白表达的改变可能会对癌细胞的生物学产生影响。本研究检测了Crm 1、Karyopherin β1（Kpnβ1）和Karyopherin α2（Kpnα2）在宫颈组织和细胞系中的表达。这些蛋白质对癌细胞的功能意义使用单独的siRNA来抑制它们的表达。基因芯片、定量RT-PCR和免疫荧光检测显示，Crm 1、Kpnβ1和Kpnα2在宫颈癌组织中的表达均显著高于正常组织。与正常细胞相比，在宫颈癌细胞系中以及在转化的上皮细胞和成纤维细胞中，表达水平类似地升高。抑制癌细胞中的Crm 1和Kpnβ1可显著降低细胞增殖，而抑制Kpnα2则无影响。非癌细胞不受Crm 1和Kpnβ1抑制的影响。通过细胞周期分析和Caspase-3/7测定，癌细胞增殖的减少与subG 1群体的增加相关，表明细胞凋亡增加。Crm 1和Kpnβ1 siRNA诱导的细胞凋亡伴随着生长抑制蛋白p53、p27、p21和p18水平的增加。我们的研究结果表明，Crm 1，Kpnβ1和Kpnα2在宫颈癌中过表达，抑制Crm 1和Kpnβ1的表达，而不是Kpnα2，诱导癌细胞死亡，使Crm 1和Kpnβ1有希望作为生物标志物和潜在的抗癌治疗靶点。
The Karyopherin proteins are involved in nucleo-cytoplasmic trafficking and are critical for protein and RNA subcellular localization. Recent studies suggest they are important in nuclear envelope component assembly, mitosis and replication. Since these are all critical cellular functions, alterations in the expression of the Karyopherins may have an impact on the biology of cancer cells. In this study, we examined the expression of the Karyopherins, Crm1, Karyopherin β1 (Kpnβ1) and Karyopherin α2 (Kpnα2), in cervical tissue and cell lines. The functional significance of these proteins to cancer cells was investigated using individual siRNAs to inhibit their expression. Microarrays, quantitative RT-PCR and immunofluorescence revealed significantly higher expression of Crm1, Kpnβ1 and Kpnα2 in cervical cancer compared to normal tissue. Expression levels were similarly elevated in cervical cancer cell lines compared to normal cells, and in transformed epithelial and fibroblast cells. Inhibition of Crm1 and Kpnβ1 in cancer cells significantly reduced cell proliferation, while Kpnα2 inhibition had no effect. Noncancer cells were unaffected by the inhibition of Crm1 and Kpnβ1. The reduction in proliferation of cancer cells was associated with an increase in a subG1 population by cell cycle analysis and Caspase-3/7 assays revealed increased apoptosis. Crm1 and Kpnβ1 siRNA-induced apoptosis was accompanied by an increase in the levels of growth inhibitory proteins, p53, p27, p21 and p18. Our results demonstrate that Crm1, Kpnβ1 and Kpnα2 are overexpressed in cervical cancer and that inhibiting the expression of Crm1 and Kpnβ1, not Kpnα2, induces cancer cell death, making Crm1 and Kpnβ1 promising candidates as both biomarkers and potential anticancer therapeutic targets.
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影响因子：
12.7
作者：
Kay, P;Soeters, R;Williamson, AL
通讯作者：
Williamson, AL
影响因子：
6.4
作者：
de Wilde, Jillian;Wilting, Saskia M.;Steenbergen, Renske D. M.
通讯作者：
Steenbergen, Renske D. M.
DOI：
10.1073/pnas.97.15.8501
发表时间：
2000-07-18
影响因子：
11.1
作者：
Hietanen, S;Lain, S;Lane, DP
通讯作者：
Lane, DP
DOI：
10.1073/pnas.96.16.9112
发表时间：
1999-08-03
影响因子：
11.1
作者：
Kudo, N;Matsumori, N;Horinouchi, S
通讯作者：
Horinouchi, S
影响因子：
3.7
作者：
Klucevsek, K.;Daley, J.;Moroianu, J.
通讯作者：
Moroianu, J.