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Overexpression of IFITM1 Has Clinicopathologic Effects on Gastric Cancer and Is Regulated by an Epigenetic Mechanism.
MedLine Citation:
PMID:  22609115     Owner:  NLM     Status:  Publisher    
In an effort to identify novel genes related to the prognosis of gastric cancer, we performed gene expression profiling and found overexpressed levels of human interferon-induced transmembrane protein 1 (IFITM1). We validated the gastric cancer-specific up-regulation of IFITM1 and its association with cancer progression. We also studied its epigenetic regulation and tumorigenesis-related functions. Expression of IFITM1 was evaluated in various human gastric cancer cells and in 35 patient tumor tissues by quantitative RT-PCR and Western blot analyses. The results showed highly up-regulated IFITM1 in cancer cell lines and tissues. Furthermore, IHC studies were performed on 151 patient tissues, and a significant correlation was revealed between higher IFITM1 expression and Lauren's intestinal type (P = 0.007) and differentiated adenocarcinoma (P = 0.025). Quantitative studies of DNA methylation for 27 CpG sites in the regulatory region showed hypermethylation in cells expressing low levels of IFITM1. Methylation-dependent IFITM1 expression was confirmed further by in vitro demethylation using 5-aza-2'-deoxycytidine and luciferase assays. The functional analysis of IFITM1 by silencing of its expression with small-interfering RNA showed decreased migration and invasiveness of cancer cells, whereas its overexpression exhibited the opposite results. In this study, we demonstrated gastric cancer-specific overexpression of IFITM1 regulated by promoter methylation and the role of IFITM1 in cancer prognosis.
Jieun Lee; Sung-Ho Goh; Naaleum Song; Jung-Ah Hwang; Seungyoon Nam; Il Ju Choi; Aesun Shin; In-Hoo Kim; Mi-Ha Ju; Jin Sook Jeong; Yeon-Su Lee
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2012-5-17
Journal Detail:
Title:  The American journal of pathology     Volume:  -     ISSN:  1525-2191     ISO Abbreviation:  -     Publication Date:  2012 May 
Date Detail:
Created Date:  2012-5-21     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  0370502     Medline TA:  Am J Pathol     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Copyright Information:
Copyright © 2012 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.
Cancer Genomics Branch, Research Institute, National Cancer Center, Goyang Gyeonggi-do, Republic of Korea.
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