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Downregulation of ADAMTS8 by DNA Hypermethylation in Gastric Cancer and Its Clinical Significance

A disintegrin and metallopeptidase with thrombospondin motif type 8 (ADAMTS8), a member of the ADAMTS family, was discovered as a novel angiogenesis inhibitor. We analyzed the expression and methylation of ADAMTS8 in primary gastric tumors and gastric cancer cell lines. We also examined the relation...

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Autores principales: Chen, Jing, Zhang, Jiakui, Li, Xin, Zhang, Chundong, Zhang, Hongbin, Jin, Junzhe, Dai, Dongqiu
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Hindawi Publishing Corporation 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4963609/
https://www.ncbi.nlm.nih.gov/pubmed/27493958
http://dx.doi.org/10.1155/2016/5083841
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author Chen, Jing
Zhang, Jiakui
Li, Xin
Zhang, Chundong
Zhang, Hongbin
Jin, Junzhe
Dai, Dongqiu
author_facet Chen, Jing
Zhang, Jiakui
Li, Xin
Zhang, Chundong
Zhang, Hongbin
Jin, Junzhe
Dai, Dongqiu
author_sort Chen, Jing
collection PubMed
description A disintegrin and metallopeptidase with thrombospondin motif type 8 (ADAMTS8), a member of the ADAMTS family, was discovered as a novel angiogenesis inhibitor. We analyzed the expression and methylation of ADAMTS8 in primary gastric tumors and gastric cancer cell lines. We also examined the relationship between ADAMTS8 expression and methylation and clinicopathologic features. The results showed that the significant downregulation of ADAMTS8 mRNA expression was observed in gastric cancer cell lines and tissues, and its expression was related to invasive depth and lymph node metastasis. CpG was hypermethylated in gastric cancer cell lines MKN45, MGC803, and BGC823, as well as primary gastric cancer specimens. ADAMTS8 mRNA expression was significantly lower in methylated primary gastric tumors. A significant association was found between ADAMTS8 methylation status and lymph node metastasis in primary gastric cancer. Moreover, ADAMTS8 expression was upregulated in the gastric cancer cell lines MGC803, BGC823, and MKN45 after treatment with 5-aza-2′-deoxycytidine. Thus, our results demonstrate that expression of ADAMTS8 mRNA is significantly decreased and DNA methylation is frequent in gastric cancer. ADAMTS8 hypermethylation is associated with decreased expression in gastric cancer and may play an important role in the invasion and metastasis of gastric cancer.
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spelling pubmed-49636092016-08-04 Downregulation of ADAMTS8 by DNA Hypermethylation in Gastric Cancer and Its Clinical Significance Chen, Jing Zhang, Jiakui Li, Xin Zhang, Chundong Zhang, Hongbin Jin, Junzhe Dai, Dongqiu Biomed Res Int Research Article A disintegrin and metallopeptidase with thrombospondin motif type 8 (ADAMTS8), a member of the ADAMTS family, was discovered as a novel angiogenesis inhibitor. We analyzed the expression and methylation of ADAMTS8 in primary gastric tumors and gastric cancer cell lines. We also examined the relationship between ADAMTS8 expression and methylation and clinicopathologic features. The results showed that the significant downregulation of ADAMTS8 mRNA expression was observed in gastric cancer cell lines and tissues, and its expression was related to invasive depth and lymph node metastasis. CpG was hypermethylated in gastric cancer cell lines MKN45, MGC803, and BGC823, as well as primary gastric cancer specimens. ADAMTS8 mRNA expression was significantly lower in methylated primary gastric tumors. A significant association was found between ADAMTS8 methylation status and lymph node metastasis in primary gastric cancer. Moreover, ADAMTS8 expression was upregulated in the gastric cancer cell lines MGC803, BGC823, and MKN45 after treatment with 5-aza-2′-deoxycytidine. Thus, our results demonstrate that expression of ADAMTS8 mRNA is significantly decreased and DNA methylation is frequent in gastric cancer. ADAMTS8 hypermethylation is associated with decreased expression in gastric cancer and may play an important role in the invasion and metastasis of gastric cancer. Hindawi Publishing Corporation 2016 2016-07-14 /pmc/articles/PMC4963609/ /pubmed/27493958 http://dx.doi.org/10.1155/2016/5083841 Text en Copyright © 2016 Jing Chen et al. https://creativecommons.org/licenses/by/4.0/ This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Research Article
Chen, Jing
Zhang, Jiakui
Li, Xin
Zhang, Chundong
Zhang, Hongbin
Jin, Junzhe
Dai, Dongqiu
Downregulation of ADAMTS8 by DNA Hypermethylation in Gastric Cancer and Its Clinical Significance
title Downregulation of ADAMTS8 by DNA Hypermethylation in Gastric Cancer and Its Clinical Significance
title_full Downregulation of ADAMTS8 by DNA Hypermethylation in Gastric Cancer and Its Clinical Significance
title_fullStr Downregulation of ADAMTS8 by DNA Hypermethylation in Gastric Cancer and Its Clinical Significance
title_full_unstemmed Downregulation of ADAMTS8 by DNA Hypermethylation in Gastric Cancer and Its Clinical Significance
title_short Downregulation of ADAMTS8 by DNA Hypermethylation in Gastric Cancer and Its Clinical Significance
title_sort downregulation of adamts8 by dna hypermethylation in gastric cancer and its clinical significance
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4963609/
https://www.ncbi.nlm.nih.gov/pubmed/27493958
http://dx.doi.org/10.1155/2016/5083841
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