The effects in vitro and in vivo of somatostatin (SS) analogues are linked to the presence of specific binding sites on target cells. Estradiol (E2) may modulate the expression of SS receptors (SSTR) in some cell models, including breast cancer and pituitary cells. Aim of this study was to evaluate the effects of E2 on SSTR1-5 ligand binding domains (LBD) expression levels in prostate epithelial cells (PEC).
Methods: We investigated the effects of E2 on the expression of SSTRs and its influences on SST-analogue SOM230 treatment on a PEC line (EPN) expressing both estrogen receptors (ER) alfa and beta. SSTR proteins were evaluated by Western-blot using specific MoAb recognizing their LBD epitopes (Y-SSTRs MoAb). Starved cells were treated with 20 mM E2 or 10−6 or 10−8 SOM230 or 20 mM E2+ SOM230 (10−8 or +10−6) for 48h. Cells were differently harvested for real time RT-PCR, Western blot or FACS assays.
Results: E2 up-regulated SSTR 1, 2 and 5 mRNAs and proteins. E2 or SOM 10−6 alone induced apoptosis and decreased slightly proliferation; 20 mM E2+ SOM230 (10−8 or 10−6) combined treatment induced a stronger rate of apoptosis and a greater decrease of proliferation. The synergistic action was correlated to: a reduction in S-phase proliferation with an arrest in G0/G1 phase induced by SOM230 and increased by E2+SOM 230 co-treatment; a caspase-dependent apoptosis induced by SOM230; a reduction of bcl-2 levels induced after addition of E2 that amplified SOM230 effects at lower doses.
Conclusions: E2 induces an up-regulation of LBD of SSTR 1, 2 and 5 and potentiates the inhibitory effects of SOM230 in PEC in vitro. Thus estrogens may negatively control prostate tumorigenesis acting directly on cell growth and death and indirectly by up-regulating SSTRs.
Declaration of interest: The authors declare that there is no conflict of interest that could be perceived as prejudicing the impartiality of the research project.
Funding: This work was supported, however funding details unavailable.
05 - 09 May 2012
European Society of Endocrinology