Variable metastatic potentials correlate with differential plectin and vimentin expression in syngeneic androgen independent prostate cancer cells.
Variable metastatic potentials correlate with differential plectin and vimentin expression in syngeneic androgen independent prostate cancer cells.
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DOI：
10.1371/journal.pone.0065005
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发表时间：
2013
期刊：
影响因子：
3.7
通讯作者：
Nyalwidhe JO
中科院分区：
文献类型：
--
作者：
Burch TC;Watson MT;Nyalwidhe JO
前列腺癌是一种临床异质性疾病，从无痛无症状疾病到非常侵袭性的转移性和危及生命的疾病形式。远处转移是前列腺癌的主要致死原因。患者管理中最关键的临床挑战是识别具有发展转移性疾病风险的个体。为了解前列腺癌转移的分子机制并鉴定具有转移潜能的标志物，我们采用同量异序标记物进行相对和绝对定量标记，并结合液相色谱基质辅助激光解吸电离串联质谱多维蛋白质鉴定技术，分析了两种同基因前列腺癌细胞系PC 3-N2和PC 3-ML 2的蛋白质表达。PC 3-N2是低转移的，而PC 3-ML 2是高转移的。在分析中鉴定了总共1，756种蛋白质，其中130种蛋白质在两种细胞系中显示不同的表达水平（p<0.01）。其中，68个蛋白质被发现是显着上调，而62个显着下调，在PC 3-ML 2细胞相比，PC 3-N2细胞。通过Western印迹验证了差异表达最显着的plectin和vimentin的上调，并通过SiRNA基因沉默确定了它们与侵袭和迁移的功能相关性。据我们所知，这项研究首次证明波形蛋白和凝集素表达的上调与雄激素非依赖性PCA的侵袭和转移呈正相关。
Prostate cancer is a clinically heterogeneous disease, ranging from indolent asymptomatic disease to very aggressive metastatic and life threatening forms of the disease. Distant metastasis represents the major lethal cause of prostate cancer. The most critical clinical challenge in the management of the patients is identifying those individuals at risk of developing metastatic disease. To understand the molecular mechanisms of prostate cancer metastasis and identify markers with metastatic potential, we have analyzed protein expression in two syngeneic prostate cancer cells lines PC3-N2 and PC3-ML2 using isobaric tags for relative and absolute quantitation labeling and multi-dimensional protein identification technology liquid chromatography matrix assisted laser desorption ionization tandem mass spectrometry. PC3-N2 is lowly metastatic while PC3-ML2 highly metastatic. A total of 1,756 proteins were identified in the analyses with 130 proteins showing different expression levels (p<0.01) in the two cell lines. Out of these, 68 proteins were found to be significantly up-regulated while 62 are significantly down-regulated in PC3-ML2 cells compared with PC3-N2 cells. The upregulation of plectin and vimentin which were the most significantly differentially expressed were validated by Western blot and their functional relevance with respect to invasion and migration was determined by siRNA gene silencing. To our knowledge, this study is the first to demonstrate that up-regulation of vimentin and plectin expression positively correlates with the invasion and metastasis of androgen-independent PCA.
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影响因子：
3.2
作者：
Bausch, Dirk;Mino-Kenudson, Mari;Fernandez-del Castillo, Carlos;Warshaw, Andrew L.;Kelly, Kimberly A.;Thayer, Sarah P.
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通讯作者：
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影响因子：
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作者：
Bartholow TL;Chandran UR;Becich MJ;Parwani AV
通讯作者：
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