Cholangiocarcinomas associated with long-term inflammation express the activation-induced cytidine deaminase and germinal center-associated nuclear protein involved in immunoglobulin V-region diversification

  • Authors:
    • Waraporn Chan-On
    • Kazuhiko Kuwahara
    • Naoya Kobayashi
    • Kazutaka Ohta
    • Tatsuya Shimasaki
    • Banchob Sripa
    • Chanvit Leelayuwat
    • Nobuo Sakaguchi
  • View Affiliations

  • Published online on: August 1, 2009     https://doi.org/10.3892/ijo_00000339
  • Pages: 287-295
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Abstract

Cholangiocarcinoma (CCA) represents a model of tumor development after long-term inflammation which causes DNA damage or impairs DNA repair mechanism. AID and GANP, both appearing in antigen-driven B cells, are involved in affinity maturation of the immunoglobulin V-region with increased somatic mutation. A normal cholangiocyte line showed the induction of AID transcripts after stimulation with TNF-α, whereas ganp transcripts appeared constitutively in this cell line. Next, we examined the expression of AID and GANP in clinical CCA specimens to obtain information whether their expression levels are associated with the malignant grade of CCA. AID expression was similarly detected in the clinical cases of both well-differentiated and poorly-differentiated CCAs. On the contrary, GANP expression was detected in CCA cells at a higher level in the nucleus of poorly-differentiated CCAs with shorter survivals than in that of well-differentiated CCAs. The high and low cases of nuclear GANP expression showed no change in the frequency of the TP53 mutations, however, further investigation by in vitro experiment demonstrated that the high GANP expression caused the increased number of γH2AX foci after DNA damage by ionizing-irradiation. These results suggest that GANP is involved in regulation of DNA repair mechanism and the abnormal over-expression of GANP together with AID might be associated with rigorous DNA damage, potentially causing the malignant development of CCAs during long-term inflammation.

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August 2009
Volume 35 Issue 2

Print ISSN: 1019-6439
Online ISSN:1791-2423

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Spandidos Publications style
Chan-On W, Kuwahara K, Kobayashi N, Ohta K, Shimasaki T, Sripa B, Leelayuwat C and Sakaguchi N: Cholangiocarcinomas associated with long-term inflammation express the activation-induced cytidine deaminase and germinal center-associated nuclear protein involved in immunoglobulin V-region diversification. Int J Oncol 35: 287-295, 2009
APA
Chan-On, W., Kuwahara, K., Kobayashi, N., Ohta, K., Shimasaki, T., Sripa, B. ... Sakaguchi, N. (2009). Cholangiocarcinomas associated with long-term inflammation express the activation-induced cytidine deaminase and germinal center-associated nuclear protein involved in immunoglobulin V-region diversification. International Journal of Oncology, 35, 287-295. https://doi.org/10.3892/ijo_00000339
MLA
Chan-On, W., Kuwahara, K., Kobayashi, N., Ohta, K., Shimasaki, T., Sripa, B., Leelayuwat, C., Sakaguchi, N."Cholangiocarcinomas associated with long-term inflammation express the activation-induced cytidine deaminase and germinal center-associated nuclear protein involved in immunoglobulin V-region diversification". International Journal of Oncology 35.2 (2009): 287-295.
Chicago
Chan-On, W., Kuwahara, K., Kobayashi, N., Ohta, K., Shimasaki, T., Sripa, B., Leelayuwat, C., Sakaguchi, N."Cholangiocarcinomas associated with long-term inflammation express the activation-induced cytidine deaminase and germinal center-associated nuclear protein involved in immunoglobulin V-region diversification". International Journal of Oncology 35, no. 2 (2009): 287-295. https://doi.org/10.3892/ijo_00000339