1. Seladin-1 expression is regulated by promoter methylation in adrenal cancer
- Author
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Massimo Mannelli, Stefania Gelmini, Alessandro Peri, Cristiana Deledda, Paola Luciani, Claudio Orlando, Lisa Simi, Rosaria Arvia, and Francesca Malentacchi
- Subjects
Oxidoreductases Acting on CH-CH Group Donors ,Cancer Research ,Time Factors ,Adrenal Gland Neoplasm ,Adrenal Gland Neoplasms ,Nerve Tissue Proteins ,Biology ,Decitabine ,Polymerase Chain Reaction ,lcsh:RC254-282 ,Gene Expression Regulation, Enzymologic ,Epigenesis, Genetic ,chemistry.chemical_compound ,Cell Line, Tumor ,Gene expression ,Genetics ,Humans ,Epigenetics ,RNA, Messenger ,Enzyme Inhibitors ,Promoter Regions, Genetic ,DNA Modification Methylases ,Regulation of gene expression ,Messenger RNA ,Carcinoma ,Methylation ,DNA Methylation ,lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,Molecular biology ,Demethylating agent ,Gene Expression Regulation, Neoplastic ,chemistry ,Oncology ,DNA methylation ,Azacitidine ,Research Article - Abstract
BackgroundSeladin-1 overexpression exerts a protective mechanism against apoptosis. Seladin-1 mRNA is variably expressed in normal human tissues. Adrenal glands show the highest levels of seladin-1 expression, which are significantly reduced in adrenal carcinomas (ACC). Since up to now seladin-1 mutations were not described, we investigated whether promoter methylation could account for the down-regulation of seladin-1 expression in ACC.MethodsA methylation sensitive site was identified in the seladin-1 gene. We treated DNA extracted from two ACC cell lines (H295R and SW13) with the demethylating agent 5-Aza-2-deoxycytidine (5-Aza). Furthermore, to evaluate the presence of an epigenetic regulation also 'in vivo', seladin-1 methylation and its mRNA expression were measured in 9 ACC and in 5 normal adrenal glands.ResultsThe treatment of cell lines with 5-Aza induced a significant increase of seladin-1 mRNA expression in H295R (fold increase, F.I. = 1.8; p = 0.02) and SW13 (F.I. = 2.9; p = 0.03). In ACC, methylation density of seladin-1 promoter was higher (2682 ± 686) than in normal adrenal glands (362 ± 97; p = 0.02). Seladin-1 mRNA expression in ACC (1452 ± 196) was significantly lower than in normal adrenal glands (3614 ± 949; p = 0.01).ConclusionOn this basis, methylation could be involved in the altered pattern of seladin-1 gene expression in ACC.
- Published
- 2010