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组蛋白去乙酰化酶1和转移相关基因1的表达在食管癌发生中的作用

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

作者信息

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

机构信息

Department of Gastroenterological Surgery, Kanazawa University Hospital, Kanazawa, Ishikawa 920-8641, Japan.

Department of Surgery, Johns Hopkins Bayview Medical Center, Johns Hopkins University School of Medicine, Baltimore, MD 21224, USA.

出版信息

Oncol Lett. 2014 Aug;8(2):758-764. doi: 10.3892/ol.2014.2176. Epub 2014 May 26.

Abstract

Animal models are important for the development of novel therapies for esophageal cancer. Histone deacetylase 1 ()/metastasis-associated gene () 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.

摘要

动物模型对于食管癌新疗法的开发很重要。组蛋白去乙酰化酶1(HDAC1)/转移相关基因1(MTA1)复合物抑制p53乙酰化,从而抑制p53诱导的细胞凋亡。本研究的目的是评估HDAC1和MTA1在大鼠食管癌发生过程中的表达情况。对大鼠进行全胃切除,然后行食管空肠吻合术以诱导慢性十二指肠内容物反流性食管炎。在术后20、30、40和50周依次处死大鼠,并检查食管。进行免疫组织化学分析以评估HDAC1和MTA1的表达及定位。术后20周,观察到鳞状上皮增生性增生和巴雷特化生(BM)。而在术后30 - 50周观察到腺癌相关的BM和鳞状细胞癌。在鳞状细胞癌发生和腺癌发生的所有阶段均观察到HDAC1和MTA1的核表达,尽管在正常食管上皮中未观察到。HDAC1和MTA1的表达可能参与十二指肠食管反流诱导的食管黏膜向具有鳞状和腺分化的癌细胞的肿瘤转化。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/08b1/4081431/731371a2aead/OL-08-02-0758-g00.jpg

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