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.

Androgen receptor regulation of the seladin-1/DHCR24 gene: altered expression in prostate cancer / Lorella Bonaccorsi; Paola Luciani; Gabriella Nesi; Edoardo Mannucci; Cristiana Deledda; Francesca Dichiara; Milena Paglierani; Fabiana Rosati; Lorenzo Masieri; Sergio Serni; Marco Carini; Laura Proietti-Pannunzi; Salvatore Monti; Gianni Forti; Giovanna Danza; Mario Serio; Alessandro Peri. - In: LABORATORY INVESTIGATION. - ISSN 0023-6837. - STAMPA. - 88:(2008), pp. 1049-1056.

Androgen receptor regulation of the seladin-1/DHCR24 gene: altered expression in prostate cancer.

BONACCORSI, LORELLA;LUCIANI, PAOLA;NESI, GABRIELLA;MANNUCCI, EDOARDO;ROSATI, FABIANA;MASIERI, LORENZO;SERNI, SERGIO;CARINI, MARCO;FORTI, GIANNI;DANZA, GIOVANNA;SERIO, MARIO;PERI, ALESSANDRO
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.
2008
88
1049
1056
Lorella Bonaccorsi; Paola Luciani; Gabriella Nesi; Edoardo Mannucci; Cristiana Deledda; Francesca Dichiara; Milena Paglierani; Fabiana Rosati; Lorenzo...espandi
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Utilizza questo identificatore per citare o creare un link a questa risorsa: https://hdl.handle.net/2158/350869
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