title: DNA methylation at promoter regions of interleukin 1B, interleukin 6, and interleukin 8 in non-small cell lung cancer.
abstract: Epidemiologic and experimental evidences support the concept that inflammation promotes the development and progression of cancers. Interleukins (ILs) regulate the expression of several molecules and signaling pathways involved in inflammation. High expression of some ILs in the tumor microenvironment has been associated with a more virulent tumor phenotype. To examine the role of IL-1β, IL-6, and IL-8 in non-small cell lung cancer, we measured mRNA levels and promoter DNA methylation in a panel of cultured human lung cells (n = 23) and in matched pair lung tumor versus adjacent non-tumorous tissues (n = 24). We found that lung cancer cells or tissues had significantly different DNA methylation and mRNA levels than normal human bronchial epithelial cells or adjacent non-tumorous tissues, respectively. High DNA methylation of ILs promoters in lung cancer cells or tissues was associated with low mRNA levels. We found an inverse correlation between DNA methylation of IL1B, IL6, and IL8 gene promoters and their corresponding mRNA levels, such inverse correlation was more significant for IL1B (i.e., all cancer cell lines used in this study had a hypermethylated IL1B promoter which was associated with silencing of the gene). Our results underline for the first time the role of epigenetic modifications in the regulation of the expression of key cytokines involved in the inflammatory response during lung cancer development.
authors.affiliation: Section for Toxicology, Department of Biological and Chemical Working Environment, National Institute of Occupational Health, PO box 8149 Dep., 0033, Oslo, Norway. xavier.tekpli@stami.no
authors.forename: Xavier
authors.initials: X
authors.lastname: Tekpli
authors.forename: Nina E
authors.initials: NE
authors.lastname: Landvik
authors.forename: Kristine H
authors.initials: KH
authors.lastname: Anmarkud
authors.forename: Vidar
authors.initials: V
authors.lastname: Skaug
authors.forename: Aage
authors.initials: A
authors.lastname: Haugen
authors.forename: Shanbeh
authors.initials: S
authors.lastname: Zienolddiny
mesh_terms: D000368:Aged; D002289:Carcinoma, Non-Small-Cell Lung / Q000235:genetics* / Q000378:metabolism; D019175:DNA Methylation; D044127:Epigenesis, Genetic; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D020868:Gene Silencing; D006801:Humans; D053583:Interleukin-1beta / Q000096:biosynthesis / Q000235:genetics*; D015850:Interleukin-6 / Q000096:biosynthesis / Q000235:genetics*; D016209:Interleukin-8 / Q000096:biosynthesis / Q000235:genetics*; D008175:Lung Neoplasms / Q000235:genetics* / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D011401:Promoter Regions, Genetic; D014407:Tumor Cells, Cultured
chemical_list: C508606:CXCL8 protein, human; C508585:IL1B protein, human; C508600:IL6 protein, human; D053583:Interleukin-1beta; D015850:Interleukin-6; D016209:Interleukin-8