Overexpression of vimentin: role in the invasive phenotype in an androgen-independent model of prostate cancer.

Overexpression of vimentin: role in the invasive phenotype in an androgen-independent model of prostate cancer.
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DOI:
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发表时间:
2003-05
期刊:
影响因子:
11.2
通讯作者:
Sadmeet Singh;Skanda K. Sadacharan;S. Su;A. Belldegrun;S. Persad;G. Singh
Sadmeet Singh;Skanda K. Sadacharan;S. Su;A. Belldegrun;S. Persad;G. Singh
中科院分区:
医学1区
文献类型:
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作者:
Sadmeet Singh;Skanda K. Sadacharan;S. Su;A. Belldegrun;S. Persad;G. Singh

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雄激素敏感的LNCaP前列腺癌细胞系的侵袭性低于雄激素不敏感的细胞系。CL1,一个侵略性的,对细菌不敏感的LNCaP亚系,通过在细菌耗尽的培养基中连续传代获得,通过cDNA微阵列分析与亲本细胞系进行了比较。发现编码中间丝蛋白波形蛋白的基因在CL1亚系中高度上调。这种差异通过北方和Western印迹证实,并通过免疫荧光显微镜观察。为了评估波形蛋白对侵袭性表型的贡献,稳定转染LNCaP细胞以过表达波形蛋白,并且用波形蛋白反义构建体转染CL1细胞。使用体外侵袭测定测试转染细胞的侵袭性。我们能够证明,波形蛋白表达的组成型波形蛋白表达CL1细胞中的波形蛋白表达的减少导致其侵袭性的显着降低,但在LNCaP细胞中的波形蛋白的强制表达并没有增加其侵袭性。这些发现意味着波形蛋白的表达有助于侵袭性表型,但不能单独赋予它。
The androgen-sensitive LNCaP prostate cancer cell line is less invasive than hormone-insensitive lines. CL1, an aggressive, hormone-insensitive LNCaP subline derived by continuous passaging in hormone-depleted medium, was compared with the parental cell line by cDNA microarray analysis. The gene coding for the intermediate filament protein vimentin was found to be highly up-regulated in the CL1 subline. This difference was confirmed by Northern and Western blots and visualized by immunofluorescence microscopy. To assess the contribution of vimentin to the invasive phenotype, LNCaP cells were stably transfected to overexpress vimentin, and the CL1 cells were transfected with vimentin antisense construct. The invasiveness of the transfected cells was tested using an in vitro invasion assay. We were able to demonstrate that decreasing vimentin expression in the constitutively vimentin-expressing CL1 cells led to a significant decrease in their invasiveness but that forcing expression of vimentin in the LNCaP cells did not augment their invasiveness. These findings imply that vimentin expression contributes to the invasive phenotype but cannot confer it alone.