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Integrin α9 gene promoter is hypermethylated and downregulated in nasopharyngeal carcinoma
Department of Microbiology, Tumor and Cell Biology, Karolinska Institutet, Stockholm, Sweden; Department of Microbiology, Faculty of Life Sciences, University of Balochistan, Quetta, Pakistan.
Department of Microbiology, Tumor and Cell Biology, Karolinska Institutet, Stockholm, Sweden.
Department of Microbiology, Tumor and Cell Biology, Karolinska Institutet, Stockholm, Sweden; State Key Laboratory of Oncology in South China, and Department of Pathology, Sun Yat-Sen University Cancer Center, Guangzhou, P.R. China.
Department of Molecular Genetic Epidemiology, German Cancer Research Center (DKFZ), Heidelberg, Germany; Oncovirology Laboratory, Institut Pasteur du Maroc, Casablanca, Morocco.
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2015 (English)In: OncoTarget, ISSN 1949-2553, E-ISSN 1949-2553, Vol. 6, no 31, 31493-31507 p.Article in journal (Refereed) Published
Abstract [en]

Epigenetic silencing of tumor suppressor genes (TSGs) by promoter methylation can be an early event in the multi-step process of carcinogenesis. Human chromosome 3 contains clusters of TSGs involved in many cancer types including nasopharyngeal carcinoma (NPC), the most common cancer in Southern China. Among ten candidate TSGs identified in chromosome 3 using NotI microarray, ITGA9 and WNT7A could be validated. 5-aza-2 deoxycytidine treatment restored the expression of ITGA9 and WNT7A in two NPC cell lines. Immunostaining showed strong expression of these genes in the membrane and cytoplasm of adjacent control nasopharyngeal epithelium cells, while they were weakly expressed in NPC tumor cells. The ITGA9 promoter showed marked differentially methylation between tumor and control tissue, whereas no differentially methylation could be detected for the WNT7A promoter. The expression level of ITGA9 in NPC tumors was downregulated 4.9-fold, compared to the expression in control. ITGA9 methylation was detected by methylation specific PCR (MSP) in 56% of EBV positive NPC-cases with 100% specificity. Taken together, this suggests that ITGA9 might be a TSG in NPC that is involved in tumor cell biology. The possibility of using ITGA9 methylation as a marker for early detection of NPC should further be explored.

Place, publisher, year, edition, pages
Albany, NY, United States: Impact Journals LLC , 2015. Vol. 6, no 31, 31493-31507 p.
Keyword [en]
nasopharyngeal carcinoma; ITGA9; DNA methylation; notl microarrays; epigenetics
National Category
Clinical Medicine
URN: urn:nbn:se:liu:diva-122660DOI: 10.18632/oncotarget.5154ISI: 000363185200093OAI: diva2:871717

Funding Agencies|Cancerfonden; Cancerforeningen in Stockholm; National Natural Science Foundation of China [81202135]; Project for the Development of University of Balochistan, Quetta, Pakistan

Available from: 2015-11-16 Created: 2015-11-13 Last updated: 2015-12-10Bibliographically approved

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Zabarovsky, Eugene R.
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