title: Epigenetic alterations of gastrokine 1 gene expression in gastric cancer.
abstract: The gastrokine 1 (GKN1) protein is important for maintaining the physiological function of the gastric mucosa. GKN1 is down-regulated in gastric tumor tissues and derived cell lines and its over-expression in gastric cancer cells induces apoptosis, suggesting a possible role for the protein as a tumor suppressor. However, the mechanism by which GKN1 is inactivated in gastric cancer remains unknown. Here, we investigated the causes of GKN1 silencing to determine if epigenetic mechanisms such as histonic modification could contribute to its down-regulation. To this end, chromatin immunoprecipitation assays for the trimethylation of histone 3 at lysine 9 (H3K9triMe) and its specific histone-lysine N-methyltransferase (SUV39H1) were performed on biopsies of normal and cancerous human gastric tissues. GKN1 down-regulation in gastric cancer tissues was shown to be associated with high levels of H3K9triMe and with the recruitment of SUV39H1 to the GKN1 promoter, suggesting the presence of an epigenetic transcriptional complex that negatively regulates GKN1 expression in gastric tumors. The inhibition of histone deacetylases with trichostatin A was also shown to increase GKN1 mRNA levels. Collectively, our results indicate that complex epigenetic machinery regulates GKN1 expression at the transcriptional level, and likely at the translational level.
authors.affiliation: Department of Molecular Medicine and Medical Biotechnology, University of Naples Federico II, Naples, Italy.
authors.forename: Filomena
authors.initials: F
authors.lastname: Altieri
authors.affiliation: Department of Molecular Medicine and Medical Biotechnology, University of Naples Federico II, Naples, Italy.
authors.forename: Chiara Stella
authors.initials: CS
authors.lastname: Di Stadio
authors.affiliation: Department of Molecular Medicine and Medical Biotechnology, University of Naples Federico II, Naples, Italy.
authors.forename: Antonella
authors.initials: A
authors.lastname: Federico
authors.affiliation: Department of Molecular Medicine and Medical Biotechnology, University of Naples Federico II, Naples, Italy.
authors.forename: Giuseppina
authors.initials: G
authors.lastname: Miselli
authors.affiliation: Hospital A. Cardarelli, Nasples, Italy.
authors.forename: Maurizio
authors.initials: M
authors.lastname: De Palma
authors.affiliation: Department of Molecular Medicine and Medical Biotechnology, University of Naples Federico II, Naples, Italy.
authors.forename: Emilia
authors.initials: E
authors.lastname: Rippa
authors.affiliation: Department of Molecular Medicine and Medical Biotechnology, University of Naples Federico II, Naples, Italy.|CEINGE, Advanced Biotechnology Scarl, Naples, Italy.
authors.forename: Paolo
authors.initials: P
authors.lastname: Arcari
mesh_terms: D000368:Aged; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000235:genetics; D044127:Epigenesis, Genetic; D015870:Gene Expression; D006801:Humans; D008875:Middle Aged; D036361:Peptide Hormones / Q000096:biosynthesis / Q000235:genetics*; D013274:Stomach Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D014162:Transfection
chemical_list: C477000:GKN1 protein, human; D036361:Peptide Hormones
keywords: epigenetics; gastric cancer; gastrokine 1; histone acetylation; histone methylation