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

Cellular & Molecular Immunology volume 13, pages 484–491 (2016)Cite this article

Abstract

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.

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Acknowledgements

We thank Professor Gu Jiang (Department of Pathology, Shantou University Medical College, Shantou, China) for providing the HeLa S3 cell line. We also thank Professor Songqing Fan (The Second Xiangya Hospital, Central South University, Changsha, China) for quantifying the immunohistochemistry results.

This work was supported by the National High Technology Research and Development Program (863) of China (No. 2006AA02A404) and the National Nature Science Foundation of China (No. 30772465, No. 30973399).

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Authors and Affiliations

  1. Laboratory of Tumor Molecular Biology, Cancer Research Institute, Central South University, Changsha, 410008, Hunan, China

    Zhi Duan, Min Tang, Xinxian Weng, Wei Yi & Ya Cao

  2. Key Laboratory of Carcinogenesis and Cancer Invasion, Ministry of Education, Changsha, 410008, Hunan, China

    Zhi Duan, Min Tang, Xinxian Weng, Wei Yi & Ya Cao

  3. Key Laboratory of Carcinogenesis, Ministry of Health, Changsha, 410008, Hunan, China

    Zhi Duan, Min Tang, Xinxian Weng, Wei Yi & Ya Cao

  4. Institutes of Biology and Medical Sciences, Soochow University, Suzhou, 215123, Jiangsu, China

    Hui Zheng

  5. Department of Cardiothoracic Surgery, Center of Clinical Gene Diagnosis and Therapy, The Second Xiangya Hospital, Central South University, Changsha, 410011, Hunan, China

    Haidan Liu

  6. Department of Immunology, Xiangya Medical College, Central South University, Changsha, 410008, Hunan, China

    Ming Li

  7. The Hormel Institute, University of Minnesota, Austin, 55912, MN, USA

    Ann M. Bode

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Duan, Z., Zheng, H., Liu, H. et al. AID expression increased by TNF-α is associated with class switch recombination of Igα gene in cancers. Cell Mol Immunol 13, 484–491 (2016). https://doi.org/10.1038/cmi.2015.26

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