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.

Seladin-1 expression is regulated by promoter methylation inadrenal cancer / Simi L; Malentacchi F; Luciani P; Gelmini S; Deledda C; Arvia R; Mannelli M; Peri A; Orlando C. - In: BMC CANCER. - ISSN 1471-2407. - ELETTRONICO. - 10(2010), pp. 201-......

Seladin-1 expression is regulated by promoter methylation inadrenal cancer

SIMI, LISA;MALENTACCHI, FRANCESCA;LUCIANI, PAOLA;GELMINI, STEFANIA;DELEDDA, CRISTIANA;ARVIA, ROSARIA;MANNELLI, MASSIMO;PERI, ALESSANDRO;ORLANDO, CLAUDIO
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.
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201
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Simi L; Malentacchi F; Luciani P; Gelmini S; Deledda C; Arvia R; Mannelli M; Peri A; Orlando C
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Utilizza questo identificativo per citare o creare un link a questo documento: http://hdl.handle.net/2158/387587
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