Seladin-1 expression is regulated by promoter methylation in adrenal cancer

• Published in: BMC cancer Vol. 10; no. 1; p. 201
• Main Authors: Simi, Lisa, Malentacchi, Francesca, Luciani, Paola, Gelmini, Stefania, Deledda, Cristiana, Arvia, Rosaria, Mannelli, Massimo, Peri, Alessandro, Orlando, Claudio
• Format: Journal Article
• Language: English
• Published: England BioMed Central Ltd 13.05.2010; BioMed Central; BMC
• Subjects: Adrenal Gland Neoplasms - enzymology; Adrenal Gland Neoplasms - genetics; Azacitidine - analogs & derivatives; Azacitidine - pharmacology; Carcinoma - enzymology; Carcinoma - genetics; Cell Line, Tumor; DNA Methylation - drug effects; DNA Modification Methylases - antagonists & inhibitors; DNA Modification Methylases - metabolism; Enzyme Inhibitors - pharmacology; Enzyme kinetics; Epigenesis, Genetic - drug effects; Gene expression; Gene Expression Regulation, Enzymologic; Gene Expression Regulation, Neoplastic; Humans; Methylation; Nerve Tissue Proteins - genetics; Nerve Tissue Proteins - metabolism; Observations; Oxidoreductases Acting on CH-CH Group Donors - genetics; Oxidoreductases Acting on CH-CH Group Donors - metabolism; Physiological aspects; Polymerase Chain Reaction; Promoter Regions, Genetic - drug effects; RNA, Messenger - metabolism; Time Factors; Italy
• ISSN: 1471-2407; 1471-2407
• DOI: 10.1186/1471-2407-10-201

Seladin-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. A 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. The 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). On this basis, methylation could be involved in the altered pattern of seladin-1 gene expression in ACC.