Androgen receptor regulation of the seladin-1/DHCR24 gene: altered expression in prostate cancer.
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.
Bonaccorsi
Lorella
L
Unit of Andrology, Department of Clinical Physiopathology, Center for Transfer, High Education and Technology (DENOThe), University of Florence, Florence, Italy.
Luciani
Paola
P
Nesi
Gabriella
G
Mannucci
Edoardo
E
Deledda
Cristiana
C
Dichiara
Francesca
F
Paglierani
Milena
M
Rosati
Fabiana
F
Masieri
Lorenzo
L
Serni
Sergio
S
Carini
Marco
M
Proietti-Pannunzi
Laura
L
Monti
Salvatore
S
Forti
Gianni
G
Danza
Giovanna
G
Serio
Mario
M
Peri
Alessandro
A