Integrin α9 gene promoter is hypermethylated and downregulated in nasopharyngeal carcinoma

Nawaz, Imran (författare): Department of Microbiology, Tumor and Cell Biology, Karolinska Institutet, Stockholm, Sweden; Department of Microbiology, Faculty of Life Sciences, University of Balochistan, Quetta, Pakistan

Hu, Li-Fu (författare): Department of Microbiology, Tumor and Cell Biology, Karolinska Institutet, Stockholm, Sweden

Du, Zi-Ming (författare): 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

Moumad, Khalid (författare): Department of Molecular Genetic Epidemiology, German Cancer Research Center (DKFZ), Heidelberg, Germany; Oncovirology Laboratory, Institut Pasteur du Maroc, Casablanca, Morocco

Ignatyev, Ilya (författare): Karolinska Institutet,Department of Microbiology, Tumor and Cell Biology, Karolinska Institutet, Stockholm, Sweden

Pavlova, Tatiana V. (författare): Karolinska Institutet,Department of Microbiology, Tumor and Cell Biology, Karolinska Institutet, Stockholm, Sweden

Kashuba, Vladimir (författare): Karolinska Institutet,Department of Microbiology, Tumor and Cell Biology, Karolinska Institutet, Stockholm, Sweden

Almgren, Malin (författare): Karolinska Institutet,Department Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden; Centre for Molecular Medicine, Stockholm, Sweden

Zabarovsky, Eugene R. (författare): Linköpings universitet,Avdelningen för cellbiologi,Hälsouniversitetet,Department of Microbiology, Tumor and Cell Biology, Karolinska Institutet, Stockholm, Sweden

Ernberg, Ingemar (författare): Department of Microbiology, Tumor and Cell Biology, Karolinska Institutet, Stockholm, Sweden

(creator_code:org_t)

2015-09-08
2015
Engelska.
Ingår i: Oncotarget. - Albany, NY, United States : Impact Journals LLC. - 1949-2553. ; 6:31, s. 31493-31507

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Abstract Ämnesord

Stäng

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.

Av författaren/redakt...: Nawaz, Imran; Hu, Li-Fu; Du, Zi-Ming; Moumad, Khalid; Ignatyev, Ilya; Pavlova, Tatiana ...; visa fler...; Kashuba, Vladimi ...; Almgren, Malin; Zabarovsky, Euge ...; Ernberg, Ingemar; visa färre...

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