Document Detail


Characterization of a New Small Bowel Adenocarcinoma Cell Line and Screening of Anti-Cancer Drug against Small Bowel Adenocarcinoma.
MedLine Citation:
PMID:  25478808     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
Small bowel adenocarcinoma (SBA) is a rare, aggressive malignancy with a poor prognosis, and the mechanisms of carcinogenesis in SBA remain unclear. Our aims were to investigate the molecular mechanisms underlying SBA and to identify treatments by establishing and characterizing an SBA cell line and performing anti-cancer drug screening. SIAC1 cells, established from jejunal SBA, showed epithelial characteristics and formed organoids in 3D culture. SIAC1 cells had a heterozygous β-catenin deletion mutation, resulting in a stable β-catenin protein with enhanced Wnt/β-catenin activity. SIAC1 cells lacked MLH1 and MSH6 expression, and target genes such as TGFBR2 and ACVR2 showed frameshift mutations. Among 10 clinical SBA samples, 2 (20%) had N-terminal deletions in β-catenin, expression of mismatch repair protein was aberrant in 4 (40%), and heterozygous frameshift mutations of three target genes were found in all 10 samples. On screening assay using 140 compounds, eribulin significantly inhibited SIAC1 cell growth both in vitro and in vivo by inhibition of the Wnt/β-catenin pathway via enhanced degradation of β-catenin. In conclusion, we established an SBA cell line with molecular characteristics similar to those of clinical SBA samples, including β-catenin deletion and mismatch repair protein deficiency, that will be useful for SBA research. Eribulin might be a candidate for SBA treatment due to its inhibitory effect on Wnt/β-catenin signaling.
Authors:
Hirobumi Suzuki; Yoshihiro Hirata; Nobumi Suzuki; Sozaburo Ihara; Kosuke Sakitani; Yuka Kobayashi; Hiroto Kinoshita; Yoku Hayakawa; Atsuo Yamada; Hirotsugu Watabe; Keisuke Tateishi; Tsuneo Ikenoue; Yutaka Yamaji; Kazuhiko Koike
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2014-12-2
Journal Detail:
Title:  The American journal of pathology     Volume:  -     ISSN:  1525-2191     ISO Abbreviation:  Am. J. Pathol.     Publication Date:  2014 Dec 
Date Detail:
Created Date:  2014-12-5     Completed Date:  -     Revised Date:  2014-12-6    
Medline Journal Info:
Nlm Unique ID:  0370502     Medline TA:  Am J Pathol     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Copyright Information:
Copyright © 2014 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.
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