Differential expression of NF-κB heterodimer RelA/p50 in human urothelial carcinoma

PeerJ

article

Sankari Durairajan¹  Charles Emmanuel Jebaraj Walter¹  Mary Divya Samuel²  Dinesh Palani¹  Dicky John Davis G³  George Priya Doss C⁴  Sneha Pasupati⁴  Thanka Johnson⁵ 

[1] Department of Biotechnology, Sri Ramachandra Medical College and Research Institute;Manipal Institute of Regenerative Medicine, Manipal Academy of Higher Education ,(formerly Manipal University);Department of Bioinformatics, Sri Ramachandra Medical College and Research Institute;Department of Integrative Biology, School of Biosciences and Technology, Vellore Institute of Technology;Department of Pathology, Sri Ramachandra Medical College and Research Institute

关键词: NF-κB;    RelA (p65);    p50;    Differential expression;    Urothelial carcinoma;    Diagnosis;    Cytoscape;    Immunohistochemistry;   

DOI  :  10.7717/peerj.5563

学科分类：社会科学、人文和艺术（综合）

来源: Inra

【 摘 要 】

BackgroundUrothelial carcinoma (UC) is the fifth most common malignancy that accounts for 5% of all cancers. Diagnostic markers that predict UC progressions are inadequate. NF-κB contributes towards disease progression upon constitutive activation in many solid tumors. The nuclear localization of NF-κB indicates increased transcriptional activity while cytoplasmic localization indicates the inactive protein repository that can be utilized readily by a malignant cell. This study delineates the nuclear and cytoplasmic differential expression of NF-κB heterodimers in UC progression.MethodsThe involvement of the NF-κB proteins in UC was analyzed in silico using cytoscape. The expression of NF-κB heterodimers was analyzed by immunohistochemistry.ResultsPINA4MS app in cytoscape revealed over expression of RelA and suppression of NF-κB1 (p50 precursor) in UC whereas the expression of NF-κB target proteins remained unhindered. Immunohistochemical localization showed nuclear RelA/p50 in low grade UC whereas in high grade only RelA expression was observed. Conversely, cytoplasmic expression of RelA/p50 remained extensive across high and low grade UC tissues (p < 0.005). RelA nuclear and cytoplasmic expression (p < 0.005) was directly proportional to the disease progression. In our study, some of the high-grade UC tissues with squamous differentiation and muscle invasion had extensive nuclear p50 localization. The phenomenon of RelA/p50 expression seen increased in low-grade UC than high grade UC might be due to their interaction with other members of NF-κB family of proteins. Thus, NF-κB RelA/p50 differential expression may play a unique role in UC pathogenesis and can serve as a biomarker for diagnosis.

【 授权许可】

CC BY