title: Overexpression of IFITM1 has clinicopathologic effects on gastric cancer and is regulated by an epigenetic mechanism.
abstract: 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.
authors.affiliation: Branch of Cancer Genomics, Research Institute, National Cancer Center, Goyang Gyeonggi-do, South Korea.
authors.forename: Jieun
authors.initials: J
authors.lastname: Lee
authors.forename: Sung-Ho
authors.initials: SH
authors.lastname: Goh
authors.forename: Naaleum
authors.initials: N
authors.lastname: Song
authors.forename: Jung-Ah
authors.initials: JA
authors.lastname: Hwang
authors.forename: Seungyoon
authors.initials: S
authors.lastname: Nam
authors.forename: Il Ju
authors.initials: IJ
authors.lastname: Choi
authors.forename: Aesun
authors.initials: A
authors.lastname: Shin
authors.forename: In-Hoo
authors.initials: IH
authors.lastname: Kim
authors.forename: Mi-Ha
authors.initials: MH
authors.lastname: Ju
authors.forename: Jin Sook
authors.initials: JS
authors.lastname: Jeong
authors.forename: Yeon-Su
authors.initials: YS
authors.lastname: Lee
mesh_terms: D000230:Adenocarcinoma / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D000368:Aged; D000943:Antigens, Differentiation / Q000096:biosynthesis* / Q000235:genetics; D014408:Biomarkers, Tumor / Q000096:biosynthesis* / Q000235:genetics; D002465:Cell Movement / Q000502:physiology; D018899:CpG Islands / Q000235:genetics; D019175:DNA Methylation; D004273:DNA, Neoplasm / Q000235:genetics; D044127:Epigenesis, Genetic / Q000502:physiology*; D005260:Female; D020869:Gene Expression Profiling / Q000379:methods; D015972:Gene Expression Regulation, Neoplastic / Q000502:physiology*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009361:Neoplasm Invasiveness; D009363:Neoplasm Proteins / Q000096:biosynthesis / Q000235:genetics; D009367:Neoplasm Staging; D011379:Prognosis; D012333:RNA, Messenger / Q000235:genetics; D012334:RNA, Neoplasm / Q000235:genetics; D013274:Stomach Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D014407:Tumor Cells, Cultured; D015854:Up-Regulation / Q000502:physiology
chemical_list: D000943:Antigens, Differentiation; D014408:Biomarkers, Tumor; D004273:DNA, Neoplasm; D009363:Neoplasm Proteins; D012333:RNA, Messenger; D012334:RNA, Neoplasm; C062010:leu-13 antigen