Epigenetic status and aberrant expression of the maspin gene in human hepato-biliary tract carcinomas

Kentaro Fujisawa, Chihaya Maesawa, Ryo Sato, Kei Wada, Satoshi Ogasawara, Yuji Akiyama, Masaru Takeda, Tomohiro Fujita, Koki Otsuka, Taro Higuchi, Kazuyuki Suzuki, Kazuyoshi Saito, Tomoyuki Masuda

Research output: Contribution to journalArticlepeer-review

28 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)214-224
Number of pages11
JournalLaboratory Investigation
Volume85
Issue number2
DOIs
Publication statusPublished - 02-2005
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Pathology and Forensic Medicine
  • Molecular Biology
  • Cell Biology

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