AID expression increased by TNF-α is associated with class switch recombination of Igα gene in cancers

作     者：Zhi Duan Hui Zheng Haidan Liu Ming Li Min Tang Xinxian Weng Wei Yi Ann M. Bode Ya Cao 

作者机构：Laboratory of Tumor Molecular Biology Cancer Research Institute Central South University Changsha Hunan 410008 China Key Laboratory of Carcinogenesis and Cancer Invasion Ministry of Education Changsha Hunan 410008 China Key Laboratory of Carcinogenesis Ministry of HealthChangsha Hunan 410008 China Institutes of Biology and Medical Sciences Soochow University Suzhou Jiangsu 215123 China Department of Cardiothoracic Surgery Center of Clinical Gene Diagnosis and Therapy The Second Xiangya Hospital Central South University Changsha Hunan 410011China Department of Immunology Xiangya Medical College Central South University Changsha Hunan 410008 China The Hormel Institute.University of Minnesota Austin MN 55912 USA 

出 版 物：《Cellular & Molecular Immunology》 (中国免疫学杂志（英文版）)

年 卷 期：2016年第13卷第4期

页      面：484-491页

核心收录：

学科分类：0710[理学-生物学] 07[理学] 08[工学] 0906[农学-兽医学] 09[农学] 071007[理学-遗传学] 0901[农学-作物学] 0836[工学-生物工程] 090102[农学-作物遗传育种] 

基　　金：supported by the National High Technology Research and Development Program (863) of China 国家自然科学基金 

主　　题：immunoglobulin class switch recombination AID TNF-α 

摘      要：Recently, immunoglobulins （Igs） were unexpectedly found to be expressed in epithelial cancers. Immunoglobulin class switching or class switch recombination （CSR） is a natural biological process that alters a B cell＇s production of antibodies （immunoglobulins） from one class to another. However, the mechanism of CSR of Iggenes in cancer is still unknown. Here, we confirmed by detecting the hallmark of CSR that the Iga gene in cancer underwent CSR. Then we focused on activation-induced cytidine deaminase （AID）, a crucial factor for initiating CSR. Further studies using tumor necrosis factor （TNF）-α stimulation and specific inhibitor of NF-KB revealed that TNF-α could increase AID expression through NF-κB signaling. Finally, we demonstrated that AID could co-localize with protein kinase A and bind to the switching （Sα） region of the Igα gene. Overexpression of AID obviously enhanced Igα heavy chain expression and its binding ability to the Sa region. These findings indicated that TNF-α-induced AID expression is involved with CSR in cancer.