背景:核包络(NE),它由核外和核内膜组成,核孔复合体和核层,调节过多的细胞过程,包括那些限制癌症发展的(基因组稳定性,细胞周期调节,和细胞迁移)。因此,受损的NE在功能上与肿瘤发生有关,监测NE改变用于诊断癌症。然而,癌症进化过程中发生的NE变化的时间顺序以及它们之间的联系仍有待精确定义,由于缺乏合适的细胞模型。
方法:分析了前列腺癌进展过程中NE蛋白(laminsA/C和B1以及内核膜蛋白emerin和β-dystroglycan[β-DG])的表达和亚细胞定位,使用共聚焦显微镜和蛋白质印迹测定,和前列腺癌细胞系统,其包含RWPE-1上皮前列腺细胞和几种具有不同侵袭力的前列腺癌细胞系。
结果:核变形与层板蛋白A/C的错位和低表达,随着前列腺癌细胞系侵袭性的增加,laminB1和emerin变得更加突出。抑制层粘连蛋白A/C表达是前列腺癌演变过程中的早期事件。虽然NE蛋白的更广泛的去调节,包括β-DG,发生在转移性前列腺细胞中。
结论:发现基于RWPE-1细胞系的系统适用于NE损害与前列腺癌侵袭性的相关性以及确定前列腺癌发生过程中NE改变的时间顺序。对该细胞系统的进一步研究将有助于识别用于前列腺癌预后和诊断的生物标志物。
BACKGROUND: The nuclear envelope (NE), which is composed of the outer and inner nuclear membranes, the nuclear pore complex and the nuclear lamina, regulates a plethora of cellular processes, including those that restrict cancer development (genomic stability, cell cycle regulation, and cell migration). Thus, impaired NE is functionally related to tumorigenesis, and monitoring of NE alterations is used to diagnose cancer. However, the chronology of NE changes occurring during cancer evolution and the connection between them remained to be precisely defined, due to the lack of appropriate cell models.
METHODS: The expression and subcellular localization of NE proteins (lamins A/C and B1 and the inner nuclear membrane proteins emerin and β-dystroglycan [β-DG]) during prostate cancer progression were analyzed, using confocal microscopy and western blot assays, and a prostate cancer cell system comprising RWPE-1 epithelial prostate cells and several prostate cancer cell lines with different invasiveness.
RESULTS: Deformed nuclei and the mislocalization and low expression of lamin A/C, lamin B1, and emerin became more prominent as the invasiveness of the prostate cancer lines increased. Suppression of lamin A/C expression was an early event during prostate cancer evolution, while a more extensive deregulation of NE proteins, including β-DG, occurred in metastatic prostate cells.
CONCLUSIONS: The RWPE-1 cell line-based system was found to be suitable for the correlation of NE impairment with prostate cancer invasiveness and determination of the chronology of NE alterations during prostate carcinogenesis. Further study of this cell system would help to identify biomarkers for prostate cancer prognosis and diagnosis.