Lessard L, Bégin L R, Gleave M E, Mes-Masson A-M, Saad F
Centre de recherche du CHUM, and Institut du cancer de Montréal, 1560 Sherbrooke Est, Montréal, Québec, Canada H2L 4M1.
Br J Cancer. 2005 Oct 31;93(9):1019-23. doi: 10.1038/sj.bjc.6602796.
Several reports suggest that the canonical nuclear factor-kappaB (NF-kappaB) pathway is constitutively activated in a subset of prostate cancer cells. However, except for RelA (p65), little is known about the status of NF-kappaB transcription factors in prostate cancer tissues. To clarify the status of NF-kappaB subunits, we analysed the expression and subcellular localisation of RelA, RelB, c-Rel, p50, and p52 on tissue array sections containing respectively 344, 346, 369, 343, and 344 cores from 75 patients. The subcellular localisation of NF-kappaB factors was tested against relevant clinical parameters (preoperative prostate-specific antigen, pathological stage, and postoperative Gleason grade). With the exception of c-Rel, each subunit was detected in the nucleus of cancer cells: significant nuclear expression of RelB, RelA, p52, and p50 was seen in 26.6, 15.6, 10.7, and 10.5% of cores, respectively. Surprisingly, cores expressing both nuclear RelA and p50 canonical pathway proteins were less frequently observed than cores expressing other subunit combinations such as RelB-p52 and RelA-RelB. In addition, the nuclear localisation of RelB correlated with patient's Gleason scores (Spearman correlation: 0.167; P=0.018). The nuclear localisation of both canonical and noncanonical NF-kappaB subunits in prostate cancer cells suggests for the first time that different NF-kappaB pathways and dimers may be activated in the progression of the disease.
多项报告表明，经典核因子-κB（NF-κB）信号通路在一部分前列腺癌细胞中呈组成性激活。然而，除RelA（p65）外，对于前列腺癌组织中NF-κB转录因子的状态知之甚少。为了阐明NF-κB亚基的状态，我们分析了RelA、RelB、c-Rel、p50和p52在分别来自75例患者的包含344、346、369、343和344个组织芯的组织芯片切片上的表达及亚细胞定位。针对相关临床参数（术前前列腺特异性抗原、病理分期和术后Gleason分级）对NF-κB因子的亚细胞定位进行了检测。除c-Rel外，每个亚基均在癌细胞核中被检测到：分别在26.6%、15.6%、10.7%和10.5%的组织芯中观察到RelB、RelA、p52和p50的显著核表达。令人惊讶的是，与表达其他亚基组合（如RelB-p52和RelA-RelB）的组织芯相比，同时表达核RelA和p50经典信号通路蛋白的组织芯较少见。此外，RelB的核定位与患者的Gleason评分相关（Spearman相关性：0.167；P = 0.018）。前列腺癌细胞中经典和非经典NF-κB亚基的核定位首次表明，在疾病进展过程中可能激活不同的NF-κB信号通路和二聚体。
