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具有不同转移潜能的人前列腺癌细胞的定量蛋白质组学研究。

Quantitative proteomic study of human prostate cancer cells with different metastatic potentials.

机构信息

Department of Oncology, Shanghai East Hospital, Tongji University School of Medicine, Shanghai 200120, P.R. China.

The Key Laboratory of Pathobiology, Ministry of Education, Bethune Medical School, Jilin University, Changchun, Jilin 130021, P.R. China.

出版信息

Int J Oncol. 2016 Apr;48(4):1437-46. doi: 10.3892/ijo.2016.3378. Epub 2016 Feb 4.

Abstract

Metastatic dissemination is a feature of most cancers including prostate cancer (PCa), and is the main cause of treatment failure and mortality. The aim of the study is to explore the mechanisms of PCa metastasis and to search for potential prognostic markers using proteomics. Two-dimensional fluorescent differential gel electrophoresis (2D-DIGE) was used to quantify proteins in normal prostate epithelial cells, bone metastasis-derived PC-3 cells, and visceral metastasis-derived PC-3M cells. Metastatic potential was confirmed by flow cytometry, electron microscopy, proliferating cell nuclear antigen assay, and wound healing assay. Differential protein expression was compared between PCa cells with different metastatic potentials (LNcap, DU145, PC-3 and PC-3M) and normal prostate epithelial cells (RWPE-1). Selected candidate proteins in human prostate tissues were analyzed using GOA, UniProt and GeneCards analyses. Eighty-six proteins were differentially expressed between cell lines (>1.5-fold, P<0.05). Among them, twelve proteins were identified by MALDI-TOF-MS. One protein was upregulated in normal prostate epithelial cells, nine proteins were upregulated in PC-3, and two proteins were upregulated in PC-3M. Proteins were divided into five groups according to their functions. The SETDB1 protein was closely associated with the prognosis of PCa. Bioinformatics suggested that SETDB1 might promote PCa bone metastasis through the WNT pathway. In conclusion, SETDB1 might be associated with the development of bone metastases from PCa. Further study is necessary to assess its exact role in PCa.

摘要

转移扩散是大多数癌症(包括前列腺癌)的特征,也是治疗失败和死亡的主要原因。本研究旨在探索前列腺癌转移的机制,并利用蛋白质组学寻找潜在的预后标志物。采用二维荧光差异凝胶电泳(2D-DIGE)技术对正常前列腺上皮细胞、骨转移衍生的 PC-3 细胞和内脏转移衍生的 PC-3M 细胞中的蛋白质进行定量分析。通过流式细胞术、电子显微镜、增殖细胞核抗原检测和划痕愈合实验来确认转移潜能。比较不同转移潜能的前列腺癌细胞(LNcap、DU145、PC-3 和 PC-3M)与正常前列腺上皮细胞(RWPE-1)之间差异表达的蛋白质。使用 GOA、UniProt 和 GeneCards 分析对人前列腺组织中的候选蛋白进行分析。细胞系之间(>1.5 倍,P<0.05)有 86 种蛋白质表达差异。其中,有 12 种蛋白质通过 MALDI-TOF-MS 鉴定。在正常前列腺上皮细胞中上调 1 种蛋白,在 PC-3 中上调 9 种蛋白,在 PC-3M 中上调 2 种蛋白。根据功能将蛋白质分为五组。SETDB1 蛋白与前列腺癌的预后密切相关。生物信息学提示 SETDB1 可能通过 WNT 通路促进前列腺癌骨转移。总之,SETDB1 可能与前列腺癌骨转移的发展有关。需要进一步研究来评估其在前列腺癌中的确切作用。

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