RelB/NF-κB links cell cycle transition and apoptosis to endometrioid adenocarcinoma tumorigenesis.
RelB/NF-κB links cell cycle transition and apoptosis to endometrioid adenocarcinoma tumorigenesis.
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RelB/NF-kappaB 将细胞周期转变和细胞凋亡与子宫内膜样腺癌肿瘤发生联系起来。
DOI：
10.1038/cddis.2016.309
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发表时间：
2016-10-06
影响因子：
9
通讯作者：
中科院分区：
文献类型：
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作者：
核因子-κB （NF-κB）信号的功能障碍与许多人类恶性肿瘤有因果关系。尽管NF-κB家族基因与子宫内膜癌发生有关，但关于NF-κB信号中枢调节因子在人类子宫内膜癌（EC）中的作用的信息有限。在此，我们研究了典型和非典型NF-κB信号在子宫内膜肿瘤发生中的具体作用。我们发现NF-κB RelB蛋白在EC样本和细胞系中高表达，而RelA蛋白在子宫内膜样腺癌（EEC）中主要表达升高。此外，肿瘤细胞内生性RelB与c-Myc、cyclin D1、Bcl-2和Bcl-xL水平丰富有关，这些蛋白是EEC细胞周期转变、细胞凋亡和增殖的关键调节因子。相反，p27的表达因RelB缺失而增强。因此，人EC中增加的RelB与EEC细胞生长增强有关，导致子宫内膜细胞致瘤性。我们的研究结果表明，非典型NF-κB信号中的调节性RelB可能作为阻断EC起始的治疗靶点。
Dysfunction of nuclear factor-κB (NF-κB) signaling has been causally associated with numerous human malignancies. Although the NF-κB family of genes has been implicated in endometrial carcinogenesis, information regarding the involvement of central regulators of NF-κB signaling in human endometrial cancer (EC) is limited. Here, we investigated the specific roles of canonical and noncanonical NF-κB signaling in endometrial tumorigenesis. We found that NF-κB RelB protein, but not RelA, displayed high expression in EC samples and cell lines, with predominant elevation in endometrioid adenocarcinoma (EEC). Moreover, tumor cell-intrinsic RelB was responsible for the abundant levels of c-Myc, cyclin D1, Bcl-2 and Bcl-xL, which are key regulators of cell cycle transition, apoptosis and proliferation in EEC. In contrast, p27 expression was enhanced by RelB depletion. Thus, increased RelB in human EC is associated with enhanced EEC cell growth, leading to endometrial cell tumorigenicity. Our results reveal that regulatory RelB in noncanonical NF-κB signaling may serve as a therapeutic target to block EC initiation.
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