RRC ID 54131
Author Shiozaki A, Ariyoshi Y, Iitaka D, Kosuga T, Shimizu H, Kudou M, Konishi T, Shoda K, Arita T, Konishi H, Komatsu S, Kubota T, Fujiwara H, Okamoto K, Kishimoto M, Konishi E, Marunaka Y, Ichikawa D, Otsuji E.
Title Functional analysis and clinical significance of sodium iodide symporter expression in gastric cancer.
Journal Gastric Cancer
Abstract BACKGROUND:Recent studies have described important roles for the sodium iodide symporter (NIS) in tumor behavior. The objectives of the present study were to investigate the role of NIS in the regulation of genes involved in tumor progression and the clinicopathological significance of its expression in gastric cancer (GC).
METHODS:In human GC cell lines, knockdown experiments were conducted using NIS siRNA, and the effects on proliferation, survival, and cellular movement were analyzed. The gene expression profiles of cells were examined using a microarray analysis. An immunohistochemical analysis was performed on 145 primary tumor samples obtained from GC patients.
RESULTS:NIS was strongly expressed in MKN45 and MKN74 cells. The depletion of NIS inhibited cell proliferation, migration, and invasion and induced apoptosis. The results of the microarray analysis revealed that various interferon (IFN) signaling-related genes, such as STAT1, STAT2, IRF1, and IFIT1, were up-regulated in NIS-depleted MKN45 cells. Furthermore, the down-regulation of NIS affected the phosphorylation of MAPKs and NF-kB. Immunohistochemical staining showed that NIS was primarily located in the cytoplasm or cell membranes of carcinoma cells, and its expression was related to the histological type or venous invasion. Prognostic analyses revealed that the strong expression of NIS was associated with shorter postoperative survival.
CONCLUSIONS:These results suggest that NIS regulates tumor progression by affecting IFN signaling, and that its strong expression is related to a worse prognosis in patients with GC. These results provide an insight into the role of NIS as a mediator and/or a biomarker for GC.
Volume 22(3)
Pages 473-485
Published 2019-5-1
DOI 10.1007/s10120-018-0874-2
PII 10.1007/s10120-018-0874-2
PMID 30191346
MeSH Aged Apoptosis Biomarkers, Tumor / genetics Biomarkers, Tumor / metabolism* Cell Movement* Cell Proliferation* Female Follow-Up Studies Gene Expression Profiling Gene Expression Regulation, Neoplastic* Humans Male Prognosis Signal Transduction Stomach Neoplasms / genetics Stomach Neoplasms / metabolism Stomach Neoplasms / pathology* Survival Rate Symporters / genetics Symporters / metabolism* Tumor Cells, Cultured
IF 7.088
Times Cited 3
Human and Animal Cells Kato III(RCB2088) HGC-27(RCB0500) NUGC-4(RCB1939) MKN45(RCB1001) MKN74(RCB1002)