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Endocrine Unit (P.L., P.F., C.C., S.B., M.S., M.M., A.P.), Department of Clinical Physiopathology and Department of Human Pathology and Oncology (G.N.), University of Florence, 50139 Florence, Italy; Division of Endocrinology, Department of Internal Medicine (G.A.), University of Ancona, 60131 Ancona, Italy; General Surgery Unit (A.V.), Ospedale Careggi, 50134 Florence, Italy; and Department of Neurology (I.G.), Inselspital-University Hospital, 3010 Bern, Switzerland
Address all correspondence and requests for reprints to: Alessandro Peri, M.D., Ph.D., Endocrine Unit, Department of Clinical Physiopathology, University of Florence, Viale Pieraccini, 6, 50139 Florence, Italy. E-mail: a.peri{at}dfc.unifi.it.
Selective Alzheimer’s disease indicator-1 (seladin-1) is a novel gene with antiapoptotic activity that is down-regulated in vulnerable brain regions in Alzheimer’s disease. This gene encodes 3-ß-hydroxysterol 
-24-reductase (DHCR24), which converts desmosterol into cholesterol. In the adrenal cortex, increased expression of seladin-1/DHCR24, which appears to be modulated by ACTH, has been recently reported in cortisol-secreting adenomas, compared with the adjacent atrophic tissue. In our study, we measured the expression level of seladin-1/DHCR24 in cortisol- (n = 18) and aldosterone-secreting (n = 16) adrenocortical adenomas, in carcinomas (n = 17), and in normal adrenal glands (n = 8) by quantitative real-time RT-PCR. The amount of seladin-1/DHCR24 mRNA was significantly reduced in carcinomas (total RNA, 2.5 ± 0.8 pg/µg) compared with the other groups (P < 0.01). Western blot analysis confirmed the mRNA results. Similarly, in adrenal malignancies, significantly reduced levels of expression of the ACTH receptor gene were found. In the adrenal cancer cell line H295R and in primary cultures from adrenocortical cells, ACTH (1 nM) and forskolin (10 µM) effectively increased seladin-1/DHCR24 expression, confirming that seladin-1/DHCR24 is modulated by the ACTH/cAMP-driven pathway. In summary, this is the first demonstration that seladin-1/DHCR24 expression is reduced in adrenal cancer, suggesting that it might be viewed as a new potential marker of adrenal malignancies.
This work was partially supported by a grant from Associazione Italiana per la Ricerca sul Cancro.
Abbreviations: DHCR24, 3-ß-Hydroxysterol -24-reductase; seladin-1, selective Alzheimer’s disease indicator-1.
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