title: Integrin α9 gene promoter is hypermethylated and downregulated in nasopharyngeal carcinoma.
abstract: 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.
authors.affiliation: Department of Microbiology, Tumor and Cell Biology, Karolinska Institutet, Stockholm, Sweden.|Department of Microbiology, Faculty of Life Sciences, University of Balochistan, Quetta, Pakistan.
authors.forename: Imran
authors.initials: I
authors.lastname: Nawaz
authors.affiliation: Department of Microbiology, Tumor and Cell Biology, Karolinska Institutet, Stockholm, Sweden.
authors.forename: Li-Fu
authors.initials: LF
authors.lastname: Hu
authors.affiliation: 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.
authors.forename: Zi-Ming
authors.initials: ZM
authors.lastname: Du
authors.affiliation: Department of Molecular Genetic Epidemiology, German Cancer Research Center (DKFZ), Heidelberg, Germany.|Oncovirology Laboratory, Institut Pasteur du Maroc, Casablanca, Morocco.
authors.forename: Khalid
authors.initials: K
authors.lastname: Moumad
authors.affiliation: Department of Microbiology, Tumor and Cell Biology, Karolinska Institutet, Stockholm, Sweden.
authors.forename: Ilya
authors.initials: I
authors.lastname: Ignatyev
authors.affiliation: Department of Microbiology, Tumor and Cell Biology, Karolinska Institutet, Stockholm, Sweden.
authors.forename: Tatiana V
authors.initials: TV
authors.lastname: Pavlova
authors.affiliation: Department of Microbiology, Tumor and Cell Biology, Karolinska Institutet, Stockholm, Sweden.
authors.forename: Vladimir
authors.initials: V
authors.lastname: Kashuba
authors.affiliation: Department Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden.|Centre for Molecular Medicine, Stockholm, Sweden.
authors.forename: Malin
authors.initials: M
authors.lastname: Almgren
authors.affiliation: Department of Microbiology, Tumor and Cell Biology, Karolinska Institutet, Stockholm, Sweden.|Department of Clinical & Experimental Medicine, Division of Cell Biology, Linköping University, Linköping, Sweden.
authors.forename: Eugene R
authors.initials: ER
authors.lastname: Zabarovsky
authors.affiliation: Department of Microbiology, Tumor and Cell Biology, Karolinska Institutet, Stockholm, Sweden.
authors.forename: Ingemar
authors.initials: I
authors.lastname: Ernberg
mesh_terms: D000964:Antimetabolites, Antineoplastic / Q000494:pharmacology; D001374:Azacitidine / Q000031:analogs & derivatives / Q000494:pharmacology; D015153:Blotting, Western; D002277:Carcinoma; D016022:Case-Control Studies; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D019175:DNA Methylation; D000077209:Decitabine; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D039001:Integrin alpha Chains / Q000235:genetics*; D016023:Integrins / Q000235:genetics*; D000077274:Nasopharyngeal Carcinoma; D009303:Nasopharyngeal Neoplasms / Q000235:genetics* / Q000473:pathology; D009305:Nasopharynx / Q000378:metabolism*; D011401:Promoter Regions, Genetic / Q000235:genetics*; D060888:Real-Time Polymerase Chain Reaction; D051153:Wnt Proteins / Q000235:genetics
chemical_list: D000964:Antimetabolites, Antineoplastic; C541973:ITGA9 protein, human; D039001:Integrin alpha Chains; D016023:Integrins; C092778:WNT7A protein, human; D051153:Wnt Proteins; C084613:integrin alpha9; D000077209:Decitabine; D001374:Azacitidine
keywords: DNA methylation; ITGA9; epigenetics; nasopharyngeal carcinoma; notI microarrays