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Aberrant Expression and Mutation-Inducing Activity of AID in Human Lung Cancer

  • Translational Research and Biomarkers
  • Published:
Annals of Surgical Oncology Aims and scope Submit manuscript

Abstract

Background

Activation-induced cytidine deaminase (AID) is expressed in B lymphocytes and triggers antibody diversification. Recent reports have indicated that the constitutive expression of AID in mice causes not only lymphomas, but also cancers of some organs including the lung, prompting us to investigate the expression and effect of AID on human lung cancer.

Materials and Methods

We examined AID mRNA expression in 17 lung cancer cell lines and 51 primary lung cancers using a quantitative RT-PCR analysis. Next, we established H1299 lung cancer cells stably overexpressing AID and performed a supF forward mutation assay. We then examined AID protein expression and p53 mutation in 129 primary lung cancers by an immunohistochemical analysis and PCR-SSCP and sequencing analyses, respectively.

Results

Aberrant mRNA expression of AID was detected in 29% (5 of 17) of the lung cancer cell lines and 31% (16 of 51) of the primary lung cancers. AID-overexpressing H1299 clones showed a 5.0- to 6.1-fold higher mutation frequency than an empty vector-transfected H1299 clone, and about half of the AID-induced mutations were base substitutions, indicating that AID induces gene mutations in lung cancer cells. Furthermore, an association was found between the AID protein expression level and the p53 mutation status in an analysis of 129 primary lung cancers. A further expression analysis revealed that a portion of AID is localized at the centrosomes.

Conclusion

Our current findings suggest that the aberrant expression of AID may be involved in a subset of human lung cancers as a result of its mutation-inducing activity.

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Acknowledgment

We are grateful to Dr. D.C. Gruenert (California Pacific Medical Center Research Institute, USA), Dr. T. Kaneko (Yokohama City University, School of Medicine, Japan), Dr. T. Niki (Jichi Medical University, Japan), and Dr. Y. Dobashi (Omiya Medical Center, Japan) for providing us with the cell lines. We acknowledge Ms. K. Nagura, Mr. K. Mizuno, and Ms. N. Sakamoto (Hamamatsu University School of Medicine) for their technical assistance. This work was supported by grants from the MHLW (21-1), the JSPS (22590356), the MEXT (20014007 and 221S0001), and the Smoking Research Foundation.

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Authors and Affiliations

  1. 1st Department of Pathology, Hamamatsu University School of Medicine, Hamamatsu, Japan

    Kazuya Shinmura MD, PhD, Hisaki Igarashi BS, Masanori Goto PhD, Hong Tao MD, PhD, Hidetaka Yamada PhD, Shun Matsuura MD, Mari Tajima & Haruhiko Sugimura MD, PhD

  2. Research Center for Environmental Quality Management, Kyoto University, Otsu, Japan

    Tomonari Matsuda PhD

  3. Genomics and Immunity, National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of Health, Bethesda, MD, USA

    Arito Yamane MD, PhD

  4. 1st Department of Surgery, Hamamatsu University School of Medicine, Hamamatsu, Japan

    Kazuhito Funai MD, PhD

  5. Division of Thoracic Surgery, Respiratory Disease Center, Seirei Mikatahara General Hospital, Hamamatsu, Japan

    Masayuki Tanahashi MD, PhD & Hiroshi Niwa MD, PhD

  6. Division of Pathology, Seirei Mikatahara General Hospital, Hamamatsu, Japan

    Hiroshi Ogawa MD, PhD

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  1. Kazuya Shinmura MD, PhD
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  2. Hisaki Igarashi BS
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  14. Haruhiko Sugimura MD, PhD
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Correspondence to Kazuya Shinmura MD, PhD.

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Shinmura, K., Igarashi, H., Goto, M. et al. Aberrant Expression and Mutation-Inducing Activity of AID in Human Lung Cancer. Ann Surg Oncol 18, 2084–2092 (2011). https://doi.org/10.1245/s10434-011-1568-8

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  • DOI: https://doi.org/10.1245/s10434-011-1568-8

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