title: Seladin-1 expression is regulated by promoter methylation in adrenal cancer.
abstract: BACKGROUND
  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.
  
  
  METHODS
  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.
  
  
  RESULTS
  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).
  
  
  CONCLUSIONS
  On this basis, methylation could be involved in the altered pattern of seladin-1 gene expression in ACC.
authors.affiliation: Clinical Biochemistry, Department of Clinical Physiopathology, University of Florence, viale Pieraccini 6, Florence, 50139 Italy.
authors.forename: Lisa
authors.initials: L
authors.lastname: Simi
authors.forename: Francesca
authors.initials: F
authors.lastname: Malentacchi
authors.forename: Paola
authors.initials: P
authors.lastname: Luciani
authors.forename: Stefania
authors.initials: S
authors.lastname: Gelmini
authors.forename: Cristiana
authors.initials: C
authors.lastname: Deledda
authors.forename: Rosaria
authors.initials: R
authors.lastname: Arvia
authors.forename: Massimo
authors.initials: M
authors.lastname: Mannelli
authors.forename: Alessandro
authors.initials: A
authors.lastname: Peri
authors.forename: Claudio
authors.initials: C
authors.lastname: Orlando
mesh_terms: D000310:Adrenal Gland Neoplasms / Q000201:enzymology / Q000235:genetics*; D001374:Azacitidine / Q000031:analogs & derivatives / Q000494:pharmacology; D002277:Carcinoma / Q000201:enzymology / Q000235:genetics*; D045744:Cell Line, Tumor; D019175:DNA Methylation / Q000187:drug effects; D015254:DNA Modification Methylases / Q000037:antagonists & inhibitors / Q000378:metabolism; D000077209:Decitabine; D004791:Enzyme Inhibitors / Q000494:pharmacology; D044127:Epigenesis, Genetic / Q000187:drug effects; D015971:Gene Expression Regulation, Enzymologic; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D009419:Nerve Tissue Proteins / Q000235:genetics* / Q000378:metabolism; D044925:Oxidoreductases Acting on CH-CH Group Donors / Q000235:genetics* / Q000378:metabolism; D016133:Polymerase Chain Reaction; D011401:Promoter Regions, Genetic / Q000187:drug effects; D012333:RNA, Messenger / Q000378:metabolism; D013997:Time Factors
chemical_list: D004791:Enzyme Inhibitors; D009419:Nerve Tissue Proteins; D012333:RNA, Messenger; D000077209:Decitabine; D044925:Oxidoreductases Acting on CH-CH Group Donors; C499055:DHCR24 protein, human; D015254:DNA Modification Methylases; D001374:Azacitidine
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