Prostate cancer (PCa) progression from androgen-dependent to castration-resistant disease is a process promoted by modifications of different signal transduction pathways within the tumor microenvironment. Improved understanding of PCa biology has led to new promising treatment strategies, such as activation of somatostatin receptors (SSTRs) by specific somatostatin analogs (SSAs) alone or in combination with other treatments. Since estrogen receptor beta (ERbeta) is emerging as a potential target in PCa chemoprevention and estradiol has been reported to up-regulate SSTRs in other solid tumors, aim of our study was to evaluate the effect of selective ERbeta activation on SSTRs gene expression. To this purpose, we used (i) DU145 cells as a model of human androgen-independent PCa, known to express ERbeta, SSTR1, SSTR2 and SSTR5; and (ii) 2,3-bis(4-hydroxyphenyl)-propionitrile (DPN; 10-8M) as ERbeta selective agonist. In DU145 cells, a six-day exposure to DPN enhanced SSTR1 gene expression (qPCR) by +58% vs. control (p<0.05), whereas that of SSTR2 and SSTR5 was unchanged. Eight-day DPN exposure further increased SSTR1 expression (+110% vs. control, p<0.01) and led to a slight non-significant increment of SSTR2 (+25%) and SSTR5 (+13%) expression. Interestingly, a different treatment pattern (six-day DPN followed by two-day wash-out -medium alone without DPN-) additionally increased all SSTRs expression, compared to either six- or eight-day treatment (SSTR1: +159%, p<0.001; SSTR2: +72%, p<0.001; SSTR5: +56%, p<0.05; all vs. control). In conclusion, the selective activation of ERbeta appears to up-regulate the gene expression of the most relevant SSTRs in PCa DU145 cells, leading us to speculate that this effect may facilitate the ability of specific SSAs to inhibit PCa cell growth.

L’attivazione selettiva di ERbeta in cellule di carcinoma prostatico promuove una iper-espressione dei recettori di somatostatina / C. Macchi, B. Morlotti, M. Arvigo, A. Colciago, D. Ferone, P. Negri Cesi, P. Magni, M. Ruscica. ((Intervento presentato al 11. convegno Società Italiana di Andrologia e Medicina della Sessualità tenutosi a Cagliari nel 2014.

L’attivazione selettiva di ERbeta in cellule di carcinoma prostatico promuove una iper-espressione dei recettori di somatostatina

C. Macchi;A. Colciago;P. Negri Cesi;P. Magni;M. Ruscica
2014

Abstract

Prostate cancer (PCa) progression from androgen-dependent to castration-resistant disease is a process promoted by modifications of different signal transduction pathways within the tumor microenvironment. Improved understanding of PCa biology has led to new promising treatment strategies, such as activation of somatostatin receptors (SSTRs) by specific somatostatin analogs (SSAs) alone or in combination with other treatments. Since estrogen receptor beta (ERbeta) is emerging as a potential target in PCa chemoprevention and estradiol has been reported to up-regulate SSTRs in other solid tumors, aim of our study was to evaluate the effect of selective ERbeta activation on SSTRs gene expression. To this purpose, we used (i) DU145 cells as a model of human androgen-independent PCa, known to express ERbeta, SSTR1, SSTR2 and SSTR5; and (ii) 2,3-bis(4-hydroxyphenyl)-propionitrile (DPN; 10-8M) as ERbeta selective agonist. In DU145 cells, a six-day exposure to DPN enhanced SSTR1 gene expression (qPCR) by +58% vs. control (p<0.05), whereas that of SSTR2 and SSTR5 was unchanged. Eight-day DPN exposure further increased SSTR1 expression (+110% vs. control, p<0.01) and led to a slight non-significant increment of SSTR2 (+25%) and SSTR5 (+13%) expression. Interestingly, a different treatment pattern (six-day DPN followed by two-day wash-out -medium alone without DPN-) additionally increased all SSTRs expression, compared to either six- or eight-day treatment (SSTR1: +159%, p<0.001; SSTR2: +72%, p<0.001; SSTR5: +56%, p<0.05; all vs. control). In conclusion, the selective activation of ERbeta appears to up-regulate the gene expression of the most relevant SSTRs in PCa DU145 cells, leading us to speculate that this effect may facilitate the ability of specific SSAs to inhibit PCa cell growth.
Estrogen receptor beta and somatostatin
Settore MED/04 - Patologia Generale
Settore MED/05 - Patologia Clinica
Settore BIO/09 - Fisiologia
L’attivazione selettiva di ERbeta in cellule di carcinoma prostatico promuove una iper-espressione dei recettori di somatostatina / C. Macchi, B. Morlotti, M. Arvigo, A. Colciago, D. Ferone, P. Negri Cesi, P. Magni, M. Ruscica. ((Intervento presentato al 11. convegno Società Italiana di Andrologia e Medicina della Sessualità tenutosi a Cagliari nel 2014.
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/2434/251556
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