Duan Zhi, Zheng Hui, Liu Haidan, Li Ming, Tang Min, Weng Xinxian, Yi Wei, Bode Ann M, Cao Ya
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.
Cell Mol Immunol. 2016 Jul;13(4):484-91. doi: 10.1038/cmi.2015.26. Epub 2015 Apr 6.
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 Ig genes in cancer is still unknown. Here, we confirmed by detecting the hallmark of CSR that the Igα 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-κB 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 Sα region. These findings indicated that TNF-α-induced AID expression is involved with CSR in cancer.
最近，人们意外地发现免疫球蛋白（Igs）在上皮癌中表达。免疫球蛋白类别转换或类别转换重组（CSR）是一种自然生物学过程，可将B细胞产生的抗体（免疫球蛋白）从一类转换为另一类。然而，癌症中Ig基因的CSR机制仍然未知。在此，我们通过检测CSR的标志证实癌症中的Igα基因发生了CSR。然后我们聚焦于激活诱导的胞嘧啶脱氨酶（AID），这是启动CSR的关键因素。使用肿瘤坏死因子（TNF）-α刺激和NF-κB特异性抑制剂的进一步研究表明，TNF-α可通过NF-κB信号通路增加AID表达。最后，我们证明AID可与蛋白激酶A共定位并结合至Igα基因的转换（Sα）区域。AID的过表达明显增强了Igα重链表达及其与Sα区域的结合能力。这些发现表明，TNF-α诱导的AID表达与癌症中的CSR有关。
