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Open Access Research article

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

Lisa Simi1, Francesca Malentacchi1, Paola Luciani2, Stefania Gelmini1, Cristiana Deledda2, Rosaria Arvia1, Massimo Mannelli2, Alessandro Peri2 and Claudio Orlando1*

Author Affiliations

1 Clinical Biochemistry, Department of Clinical Physiopathology, University of Florence, viale Pieraccini 6, Florence, 50139 Italy

2 Endocrinology Units, Department of Clinical Physiopathology, University of Florence, viale Pieraccini 6, Florence, 50139 Italy

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BMC Cancer 2010, 10:201  doi:10.1186/1471-2407-10-201

Published: 13 May 2010

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).

Conclusion

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