p52 expression enhances lung cancer progression.
p52 expression enhances lung cancer progression.
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DOI：
10.1038/s41598-018-24488-8
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发表时间：
2018-04-17
影响因子：
4.6
通讯作者：
Blackwell TS
中科院分区：
文献类型：
--
作者：
Saxon JA;Yu H;Polosukhin VV;Stathopoulos GT;Gleaves LA;McLoed AG;Massion PP;Yull FE;Zhao Z;Blackwell TS
虽然许多研究表明经典NF-κB信号转导是肺癌发生的中心途径，但非经典NF-κB信号转导在肺癌中的作用仍不明确。我们观察到非典型NF-κB组分p100/p52在人肺腺癌中频繁的核积聚。为了研究非经典NF-κB信号转导对肺癌发生的影响，我们采用了在气道上皮细胞中强力霉素诱导表达p52的转基因小鼠。p52过表达导致肿瘤数量增加，并在注射致癌物乌拉坦后进展。对转基因小鼠肺组织的基因表达分析结合体外研究表明，p52通过调节细胞周期相关基因促进肺上皮细胞增殖。使用来自癌症基因组图谱（TCGA）数据库的基因表达和患者信息，我们发现肺腺癌中p52相关基因的表达增加，并与生存率降低相关，即使在早期疾病中也是如此。对其他人肺腺癌数据集中p52相关基因表达的分析证实了这些发现。总之，这些研究暗示了非经典NF-κB组分p52在肺癌发生中的作用，并建议调节p52活性和/或下游介质作为新的治疗靶点。
While many studies have demonstrated that canonical NF-κB signaling is a central pathway in lung tumorigenesis, the role of non-canonical NF-κB signaling in lung cancer remains undefined. We observed frequent nuclear accumulation of the non-canonical NF-κB component p100/p52 in human lung adenocarcinoma. To investigate the impact of non-canonical NF-κB signaling on lung carcinogenesis, we employed transgenic mice with doxycycline-inducible expression of p52 in airway epithelial cells. p52 over-expression led to increased tumor number and progression after injection of the carcinogen urethane. Gene expression analysis of lungs from transgenic mice combined with in vitro studies suggested that p52 promotes proliferation of lung epithelial cells through regulation of cell cycle-associated genes. Using gene expression and patient information from The Cancer Genome Atlas (TCGA) database, we found that expression of p52-associated genes was increased in lung adenocarcinomas and correlated with reduced survival, even in early stage disease. Analysis of p52-associated gene expression in additional human lung adenocarcinoma datasets corroborated these findings. Together, these studies implicate the non-canonical NF-κB component p52 in lung carcinogenesis and suggest modulation of p52 activity and/or downstream mediators as new therapeutic targets.
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影响因子：
32.4
作者：
Dejardin, E;Droin, NM;Green, DR
通讯作者：
Green, DR
DOI：
10.1158/1078-0432.ccr-13-0341
发表时间：
2013-07-01
期刊：
Clinical cancer research : an official journal of the American Association for Cancer Research
影响因子：
--
作者：
Kabbout M;Garcia MM;Fujimoto J;Liu DD;Woods D;Chow CW;Mendoza G;Momin AA;James BP;Solis L;Behrens C;Lee JJ;Wistuba II;Kadara H
通讯作者：
Kadara H
影响因子：
4.5
作者：
Iannetti A;Ledoux AC;Tudhope SJ;Sellier H;Zhao B;Mowla S;Moore A;Hummerich H;Gewurz BE;Cockell SJ;Jat PS;Willmore E;Perkins ND
通讯作者：
Perkins ND
影响因子：
3.7
作者：
Giopanou I;Lilis I;Papaleonidopoulos V;Marazioti A;Spella M;Vreka M;Papadaki H;Stathopoulos GT
通讯作者：
Stathopoulos GT
DOI：
10.1084/jem.187.2.147
发表时间：
1998-01-19
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Franzoso G;Carlson L;Poljak L;Shores EW;Epstein S;Leonardi A;Grinberg A;Tran T;Scharton-Kersten T;Anver M;Love P;Brown K;Siebenlist U
通讯作者：
Siebenlist U