Altered expression of MUTYH and an increase in 8-hydroxydeoxyguanosine are early events in ulcerative colitis-associated carcinogenesis

Masaki Gushima, Minako Hirahashi, Takayuki Matsumoto, Kouhei Fujita, Ritsuko Fujisawa, Kazuhiro Mizumoto, Yusaku Nakabeppu, Mitsuo Iida, Takashi Yao, Masazumi Tsuneyoshi

研究成果: Contribution to journalArticle査読

28 被引用数 (Scopus)

抄録

8-Hydroxy-guanine (8-OH-G) mismatches readily with adenine residues, leading to a G:C to T:A transversion mutation. The human mutY homologue (MUTYH) excises adenine misincorporated opposite 8-OH-G during replication and suppresses mutations caused by reactive oxygen species. We defined the expression of 8-hydroxydeoxyguanosine (8-OHdG) and MUTYH in ulcerative colitis (UC)-associated neoplasia by immunohistochemistry and compared this with expression in UC patients without neoplasia and patients unaffected by UC. We also performed mutation analyses for MUTYH and K-ras. 8-OHdG was expressed more intensely in the mucosa of UC-associated neoplasia and UC without neoplasm than in the mucosa unaffected by UC. Immunohistochemistry with two different types of MUTYH antibody showed that UC-associated neoplasia and UC without neoplasia exhibited strong cytoplasmic expression and attenuated nuclear expression of MUTYH when compared with patients unaffected by UC. No pathological MUTYH mutations were detected in any of the UC-associated neoplasia cases. However, K-ras mutation was detected in two cases, one of which showed G:C to T:A transversion mutation and attenuated nuclear staining of MUTYH. In conclusion, inflamed mucosa of UC is exposed to oxidative damage. An increase in cytoplasmic MUTYH, rather than its mutation, may contribute to the promotion of carcinogenesis in UC.

本文言語英語
ページ(範囲)77-86
ページ数10
ジャーナルJournal of Pathology
219
1
DOI
出版ステータス出版済み - 9 2009

All Science Journal Classification (ASJC) codes

  • 病理学および法医学

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