title: Global histone modification of histone H3 in colorectal cancer and its precursor lesions.
abstract: Chromatin remodeling through histone modification is an important mechanism of epigenetic gene dysregulation in human cancers. However, little is known about global alteration of histone status during tumorigenesis and cancer progression. Histone H3 status was examined in benign and malignant colorectal tumors by immunohistochemistry and Western blotting. For immunohistochemical evaluation, 4 anti-histone H3 antibodies, specific to dimethylation at lysine 4 (H3K4me2), acetylation at lysine 9 (H3K9ac), dimethylation at lysine 9 (H3K9me2), and trimethylation at lysine 27 (H3K27me3), were used. On immunohistochemistry, H3K4me2, H3K9ac, and H3K27me3 showed no significant changes between normal and colorectal tumors. On the other hand, the global level of H3K9me2 was distinctly higher in neoplastic cells (adenoma and adenocarcinoma) than in normal glandular cells. In addition, it was significantly higher in adenocarcinoma than in adenoma. Correspondingly, Western blotting confirmed that H3K9me2 expression was significantly higher in adenocarcinomas than in normal colorectal mucosa. No alteration of H3K9me2 was observed with tumor differentiation and with the histological subtypes of colorectal cancers. These results suggest that aberration of the global H3K9me2 level is an important epigenetic event in colorectal tumorigenesis and carcinogenesis involved with gene regulation in neoplastic cells through chromatin remodeling.
authors.affiliation: Department of Pathology, Interdisciplinary Graduate School of Medicine and Engineering, University of Yamanashi, Yamanashi 409-3898, Japan. tadaon@yamanashi.ac.jp
authors.forename: Tadao
authors.initials: T
authors.lastname: Nakazawa
authors.forename: Tetsuo
authors.initials: T
authors.lastname: Kondo
authors.forename: Defu
authors.initials: D
authors.lastname: Ma
authors.forename: Dongfeng
authors.initials: D
authors.lastname: Niu
authors.forename: Kunio
authors.initials: K
authors.lastname: Mochizuki
authors.forename: Tomonori
authors.initials: T
authors.lastname: Kawasaki
authors.forename: Tetsu
authors.initials: T
authors.lastname: Yamane
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Iino
authors.forename: Hideki
authors.initials: H
authors.lastname: Fujii
authors.forename: Ryohei
authors.initials: R
authors.lastname: Katoh
mesh_terms: D000230:Adenocarcinoma / Q000235:genetics* / Q000378:metabolism; D000236:Adenoma / Q000235:genetics* / Q000378:metabolism; D015153:Blotting, Western; D015179:Colorectal Neoplasms / Q000235:genetics* / Q000378:metabolism; D019175:DNA Methylation; D044127:Epigenesis, Genetic; D006657:Histones / Q000378:metabolism*; D006801:Humans; D007150:Immunohistochemistry; D011230:Precancerous Conditions / Q000235:genetics / Q000378:metabolism
chemical_list: D006657:Histones