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

Kazuya Shinmura MD, PhD, Hisaki Igarashi BS, Masanori Goto PhD, Hong Tao MD, PhD, Hidetaka Yamada PhD, Shun Matsuura MD, Mari Tajima, Tomonari Matsuda PhD, Arito Yamane MD, PhD, Kazuhito Funai MD, PhD, Masayuki Tanahashi MD, PhD, Hiroshi Niwa MD, PhD, Hiroshi Ogawa MD, PhD, Haruhiko Sugimura MD, PhD
Translational Research and Biomarkers
Volume 18, Issue 7 / July , 2011

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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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