Impact of histone deacetylase 1 and metastasis-associated gene 1 expression in esophageal carcinogenesis

Tomoharu Miyashita, Hidehiro Tajima, Masayoshi Munemoto, Furhawn A. Shah, John W. Harmon, Toshifumi Watanabe, Masatoshi Shoji, Koichi Okamoto, Shinichi Nakanuma, Seisho Sakai, Jun Kinoshita, Isamu Makino, Keishi Nakamura, Hironori Hayashi, Katsunobu Oyama, Masafumi Inokuchi, Hisatoshi Nakagawara, Hiroyuki Takamura, Itasu Ninomiya, Hirohisa KitagawaSachio Fushida, Kenichi Mukaisho, Takashi Fujimura, Tetsuo Ohta

Research output: Contribution to journalArticle

Abstract

Animal models are important for the development of novel therapies for esophageal cancer. Histone deacetylase 1 (HDAC1)/metastasis-associated gene (MTA1) complexes inhibit p53 acetylation and thus, inhibit p53-induced apoptosis. The aim of the present study was to evaluate HDAC1 and MTA1 expression in esophageal carcinogenesis in rats. The rats underwent a total gastrectomy followed by esophagojejunostomy to induce chronic duodenal content reflux esophagitis. The rats were sacrificed sequentially at 20, 30, 40 and 50 weeks post-surgery and the esophagi were examined. Immunohistochemical analysis was conducted to assess the expression and localization of HDAC1 and MTA1. At 20 weeks post-surgery, squamous proliferative hyperplasia and Barrett's metaplasia (BM) were observed. While, adenocarcinoma-associated BM and squamous cell carcinoma were observed at 30-50 weeks post-surgery. The nuclear expression of HDAC1 and MTA1 was observed in all of the stages of squamous carcinogenesis and adenocarcinogenesis, although not in the normal esophageal epithelium. The expression of HDAC1 and MTA1 may be involved in duodenoesophageal reflux-induced neoplastic transformation of the esophageal mucosa into cancer cells with squamous and adeno differentiation.

Original languageEnglish (US)
Pages (from-to)758-764
Number of pages7
JournalOncology Letters
Volume8
Issue number2
DOIs
StatePublished - Aug 2014

Keywords

  • Barrett's esophagus
  • Esophageal adenocarcinoma
  • Esophageal carcinogenesis
  • Histone deacetylases
  • Metastasis-associated gene

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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  • Cite this

    Miyashita, T., Tajima, H., Munemoto, M., Shah, F. A., Harmon, J. W., Watanabe, T., Shoji, M., Okamoto, K., Nakanuma, S., Sakai, S., Kinoshita, J., Makino, I., Nakamura, K., Hayashi, H., Oyama, K., Inokuchi, M., Nakagawara, H., Takamura, H., Ninomiya, I., ... Ohta, T. (2014). Impact of histone deacetylase 1 and metastasis-associated gene 1 expression in esophageal carcinogenesis. Oncology Letters, 8(2), 758-764. https://doi.org/10.3892/ol.2014.2176