1. ¹Unit of Andrology, Department of Clinical Physiopathology, Center for Transfer, High Education and Technology (DENOThe), University of Florence, Florence, Italy
2. ²Unit of Endocrinology, Department of Clinical Physiopathology, Center for Transfer, High Education and Technology (DENOThe), University of Florence, Florence, Italy
3. ³Department of Human Pathology and Oncology, University of Florence, Florence, Italy
4. ⁴Geriatric Cardiology, Careggi University Hospital, Florence, Italy
5. ⁵Unit of Urology, Department of Critical Care Medicine and Surgery, University of Florence, Florence, Italy
6. ⁶Unit of Endocrinology, Sant'Andrea Hospital UOC, II University of Rome 'La Sapienza', Rome, Italy

Correspondence: Professor A Peri, MD, PhD, Unit of Endocrinology, Department of Clinical Physiopathology, Center for Transfer, High Education and Technology (DENOThe), University of Florence, Viale Pieraccini, 6, 50139 Florence, Italy. E-mail: a.peri@dfc.unifi.it

⁷These authors contributed equally to this work.

Received 13 February 2008; Revised 3 June 2008; Accepted 11 June 2008; Published online 1 September 2008.

Abstract

Prostate cancer (CaP) represents a major leading cause of morbidity and mortality in the Western world. Elevated cholesterol levels, resulting from altered cholesterol metabolism, have been found in CaP cells. Seladin-1 (SELective Alzheimer Disease INdicator-1)/DHCR24 is a recently described gene involved in cholesterol biosynthesis. Here, we demonstrated the androgen regulation of seladin-1/DHCR24 expression, due to the presence of androgen responsive element sequences in its promoter region. In metastatic androgen receptor-negative CaP cells seladin-1/DHCR24 expression and cholesterol amount were reduced compared to androgen receptor-positive cells. In tumor samples from 61 patients who underwent radical prostatectomy the expression of seladin-1/DHCR24 was significantly higher with respect to normal tissues. In addition, in cancer tissues mRNA levels were positively related to T stage. In tumor specimens from 23 patients who received androgen ablation treatment for 3 months before surgery seladin-1/DHCR24 expression was significantly lower with respect to patients treated by surgery only. In conclusion, our study demonstrated for the first time the androgen regulation of the seladin-1/DHCR24 gene and the presence of a higher level of expression in CaP tissues, compared to the normal prostate. These findings, together with the results previously obtained in metastatic disease, suggest an involvement of this gene in CaP.