Human prostate cancer (PC) is an androgen(A)-sensitive disease pharmacologically controlled by A-blockade. However, this therapy often induces the growth of A-independent PC and increased invasiveness. Recently, we found that dihydrotestosterone inhibits PC cell migration through the conversion to its metabolite 5alpha-androstane-3beta,17beta-diol (3beta-Adiol), which is unable to bind A-receptor, but interacts with the estrogen receptor beta (ERbeta). Aims of the study were to investigate the role of 3beta-Adiol in PC progression. Studies performed on human A-independent PC3 cells demonstrated that 3beta-Adiol, but not estradiol, 1) decreases cell proliferation; 2) inhibits cell detachment and 3) cell invasion. 4) In nude mice both subcutaneously implanted and orthotopically engrafted with PC3-luciferase cells, 3beta-Adiol reduced PC3 growth in vivo as assessed by photon imaging. In conclusions, these data demonstrate that 3beta-Adiol is an effective agent against human prostate cancer development. The estrogenic effect of testosterone derivatives (ERbeta-dependent) inhibits not only cell migration, but also invasion and may be protective against PC invasion and metastasis.
Role of estrogen receptor beta in the progression of prostate cancer / D. Dondi, A. Biserni, M. Piccolella, A. Maggi, D. Sau, P. Ciana, A. Poletti. ((Intervento presentato al 10. convegno Annual Congress FISV - Federazione Italiana Scienze della Vita tenutosi a Riva del Garda nel 2008.
Role of estrogen receptor beta in the progression of prostate cancer
D. DondiPrimo
;A. BiserniSecondo
;M. Piccolella;A. Maggi;D. Sau;P. Ciana;A. PolettiUltimo
2008
Abstract
Human prostate cancer (PC) is an androgen(A)-sensitive disease pharmacologically controlled by A-blockade. However, this therapy often induces the growth of A-independent PC and increased invasiveness. Recently, we found that dihydrotestosterone inhibits PC cell migration through the conversion to its metabolite 5alpha-androstane-3beta,17beta-diol (3beta-Adiol), which is unable to bind A-receptor, but interacts with the estrogen receptor beta (ERbeta). Aims of the study were to investigate the role of 3beta-Adiol in PC progression. Studies performed on human A-independent PC3 cells demonstrated that 3beta-Adiol, but not estradiol, 1) decreases cell proliferation; 2) inhibits cell detachment and 3) cell invasion. 4) In nude mice both subcutaneously implanted and orthotopically engrafted with PC3-luciferase cells, 3beta-Adiol reduced PC3 growth in vivo as assessed by photon imaging. In conclusions, these data demonstrate that 3beta-Adiol is an effective agent against human prostate cancer development. The estrogenic effect of testosterone derivatives (ERbeta-dependent) inhibits not only cell migration, but also invasion and may be protective against PC invasion and metastasis.Pubblicazioni consigliate
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