The involvement of aberrant AID expression in human gingival epithelial cells with Streptococcus anginosus antigen on the mechanisms of oral cancer.

2019 Fiscal Year Final Research Report

• Project/Area Number: 17K11623
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Morphological basic dentistry
• Research Institution: Iwate Medical University
• Principal Investigator: Sasaki Minoru 岩手医科大学, 歯学部, 教授 (40187133)
• Co-Investigator(Kenkyū-buntansha): 石河 太知 岩手医科大学, 歯学部, 助教 (10569247) ; 下山 佑 岩手医科大学, 歯学部, 講師 (90453331)
• Project Period (FY): 2017-04-01 – 2020-03-31
• Keywords: AID / Streptococcus anginosus / bacterial infection / carcinogenesis

Outline of Final Research Achievements

In this study, the aberrant AID expressions in the primary cultured gingival epithelial cells after stimulation with SAA, a bioactive antigen of S. anginosus, was investigated. The stimulation of the cultured cells with SAA could induce the NF-kB activation and aberrant AID expression in all the epithelial cells tested, and the addition of an inhibitor of NF-kB activation abrogated the aberrant AID expression. In addition, to identify the proteins in bioactive fractions of SAA, we used proteome analysis with two-dimensional gel electrophoresis and LC-MS/MS. The SAA was identified to tyrosine aminoacyl-tRNA synthetase. When the recombinant protein of SAA stimulated the macrophage cell line, J774.1, this recombinant protein produced NO and expressed induced NO synthetase (iNOS) mRNA. Thus, S. anginosus infection could be closely related with squamous cell carcinoma.

Free Research Field

分子微生物学

Academic Significance and Societal Importance of the Research Achievements

放射線，化学物質およびウイルス感染という発癌因子に比べ，細菌感染による発癌研究の歴史は浅い．これまでは感染によって過剰に産生される活性酸素や一酸化窒素などの分子によるDNAへの傷害が発癌要因の中心と考えられてきた．本研究により，S.anginosus感染により遺伝子を直接変異させる能力のある酵素“AID”の発現，動態が明らかとなり，生物発癌発症機序の研究領域へ波及効果が期待できる．さらに，口腔癌予防ワクチンとしてのS. anginosusのSAAを用いた粘膜ワクチンやAID活性化阻害剤による口腔癌治療薬の開発につながることも期待される．