Potential Cross-Talk between Alternative and Classical NF-κB Pathways in Prostate Cancer Tissues as Measured by a Multi-Staining Immunofluorescence Co-Localization Assay.
Potential Cross-Talk between Alternative and Classical NF-κB Pathways in Prostate Cancer Tissues as Measured by a Multi-Staining Immunofluorescence Co-Localization Assay.
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DOI：
10.1371/journal.pone.0131024
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发表时间：
2015
期刊：
影响因子：
3.7
通讯作者：
Saad F
中科院分区：
文献类型：
--
作者：
Labouba I;Le Page C;Communal L;Kristessen T;You X;Péant B;Barrès V;Gannon PO;Mes-Masson AM;Saad F
虽然已知经典的NF-κB/p65通路参与前列腺癌进展并与患者预后不良相关，但NF-κB /RelB替代蛋白的作用尚未明确。在此，我们分析了前列腺癌组织中NF-κB通路的激活，并将这种激活与疾病的临床特征相关联。采用多重免疫荧光技术同时定量观察200例石蜡包埋标本中p65和RelB的核定位。使用适当的荧光染料标记物定义上皮细胞，并使用自动评分系统定量所得免疫荧光信号。发现与正常邻近组织相比，肿瘤组织中p65的核频率显著增加，而RelB的频率降低（p < 0.001，Wilcoxon检验）。如前所述，p65核频率与生化复发风险相关。尽管单独的RelB核频率不能预测复发，但活化的RelB的存在降低了与p65活化相关的复发风险。首次在前列腺癌组织中评估了p65/RelB共分布，并提示在前列腺癌进展中两种NF-κB途径之间存在负串扰。
While the classical NF-κB/p65 pathway is known to be involved in prostate cancer progression and is associated with poor patient outcome, the role of the NF-κB /RelB alternative protein is not well defined. Here we analyzed the activation of both NF-κB pathways in prostate cancer tissues and correlate this activation with clinical features of the disease. A multiple immunofluorescence technique was employed to concomitantly and quantitatively visualize the nuclear localization of p65 and RelB in 200 paraffin embedded samples. Epithelia were defined using appropriate fluorochrome markers and the resulting immunofluorescent signals were quantified with an automated scoring system. The nuclear frequency of p65 was found to be significantly increased in tumor tissues as compared with normal adjacent tissue, whereas the frequency for RelB was decreased (p < 0.001, Wilcoxon test). As previously reported, p65 nuclear frequency was associated with a risk of biochemical recurrence. Although, RelB nuclear frequency alone did not predict recurrence, the presence of activated RelB reduced the risk of recurrence associated with the activation of p65. For the first time p65/RelB co-distribution was assessed in prostate cancer tissues and suggested a negative crosstalk between the two NF-κB pathways in prostate cancer progression.