title: Epigenetic status and aberrant expression of the maspin gene in human hepato-biliary tract carcinomas.
abstract: We examined expression of maspin and the epigenetic status of its gene in 40 primary hepato-biliary tract carcinomas and 11 cell lines originating from hepato-pancreatico-biliary tract carcinomas. Aberrant maspin expression was frequently observed immunohistochemically in biliary tract carcinomas (22/25, 88%) but not in hepatocellular carcinomas (HCCs) (0/15, 0%). Aberrant maspin expression by five pancreatico-biliary tract carcinoma cell lines was closely associated with demethylation at the maspin promoter. Five of six HCC cell lines were maspin-negative and exhibited extensive hypomethylation and hypoacetylation at the maspin promoter. Treatment with 5-aza-2'-deoxycytidine did not activate maspin expression in these five maspin-negative HCC cell lines, whereas treatment with Trichostatin A (TSA) activated maspin expression in two of them. Treatment with TSA increased histone acetylation in some HCC cell lines. These results suggest that aberrant maspin expression in biliary tract carcinomas is closely associated with demethylation at the promoter region, but that some HCC cell lines additionally require histone acetylation. In addition, the fact that maspin-negative HCC cell lines remain after treatment with TSA suggests the existence of other repressive factors controlling maspin expression.
authors.affiliation: Department of Pathology, Iwate Medical University School of Medicine, Morioka, Japan.
authors.forename: Kentaro
authors.initials: K
authors.lastname: Fujisawa
authors.forename: Chihaya
authors.initials: C
authors.lastname: Maesawa
authors.forename: Ryo
authors.initials: R
authors.lastname: Sato
authors.forename: Kei
authors.initials: K
authors.lastname: Wada
authors.forename: Satoshi
authors.initials: S
authors.lastname: Ogasawara
authors.forename: Yuji
authors.initials: Y
authors.lastname: Akiyama
authors.forename: Masaru
authors.initials: M
authors.lastname: Takeda
authors.forename: Tomohiro
authors.initials: T
authors.lastname: Fujita
authors.forename: Koki
authors.initials: K
authors.lastname: Otsuka
authors.forename: Taro
authors.initials: T
authors.lastname: Higuchi
authors.forename: Kazuyuki
authors.initials: K
authors.lastname: Suzuki
authors.forename: Kazuyoshi
authors.initials: K
authors.lastname: Saito
authors.forename: Tomoyuki
authors.initials: T
authors.lastname: Masuda
mesh_terms: D000107:Acetylation; D001650:Bile Duct Neoplasms / Q000235:genetics* / Q000378:metabolism; D002277:Carcinoma / Q000235:genetics / Q000378:metabolism; D045744:Cell Line, Tumor; D002843:Chromatin / Q000378:metabolism; D019175:DNA Methylation; D044127:Epigenesis, Genetic; D005260:Female; D016147:Genes, Tumor Suppressor; D006801:Humans; D006877:Hydroxamic Acids / Q000494:pharmacology; D007150:Immunohistochemistry; D008113:Liver Neoplasms / Q000235:genetics* / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D010190:Pancreatic Neoplasms / Q000235:genetics / Q000378:metabolism; D011233:Precipitin Tests; D011401:Promoter Regions, Genetic; D011500:Protein Synthesis Inhibitors / Q000494:pharmacology; D011506:Proteins / Q000235:genetics* / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D017422:Sequence Analysis, DNA; D015843:Serpins / Q000235:genetics* / Q000378:metabolism*
chemical_list: D002843:Chromatin; D006877:Hydroxamic Acids; D011500:Protein Synthesis Inhibitors; D011506:Proteins; D012333:RNA, Messenger; C085344:SERPIN-B5; D015843:Serpins; C012589:trichostatin A