p52 expression enhances lung cancer progression

Saxon, Jamie A.; Yu, Hui; Polosukhin, Vasiliy V.; Stathopoulos, Georgios T.; Gleaves, Linda A.; McLoed, Allyson G.; Massion, Pierre P.; Yull, Fiona E.; Zhao, Zhongming und Blackwell, Timothy S. (2018): p52 expression enhances lung cancer progression. In: Scientific Reports, Bd. 8, 6078

Abstract

While many studies have demonstrated that canonical NF-kappa B signaling is a central pathway in lung tumorigenesis, the role of non-canonical NF-kappa B signaling in lung cancer remains undefined. We observed frequent nuclear accumulation of the non-canonical NF-kappa B component p100/p52 in human lung adenocarcinoma. To investigate the impact of non-canonical NF-kappa B 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-kappa B component p52 in lung carcinogenesis and suggest modulation of p52 activity and/or downstream mediators as new therapeutic targets.

• Dokumententyp: Zeitschriftenartikel
• Fakultät: Medizin
• Themengebiete: 600 Technik, Medizin, angewandte Wissenschaften > 610 Medizin und Gesundheit
• ISSN: 2045-2322
• Sprache: Englisch