ECE2013 Poster Presentations Endocrine tumours and neoplasia (66 abstracts)
The expression of SSTR dominant negative truncated variant sst5tMD4 influences the effects of SOM-230 on prostate cells in vitro
Valentina Rossi 1 , Daniela Visconti 3 , Cristina De Rosa 2 , Ciro Abbondanza 2 , Iolanda Cioffi 3 , Assunta De Masi 3 & Antonio Agostino Sinisi 3
1Ypsilon Biotechnology snc, Napoli, Italy; 2Dpt Patologia Generale, Second University of Napoli, Napoli, Italy; 3Dpt Scienze Cardiotoraciche e Polmonari, U. Endocrinology, Second University of Napoli, Napoli, Italy.
Introduction: The presence of truncated variant of somatostatin receptors (SSTR) has been demonstrated in pituitary tumours. These variants seems act as dominant negative of SSTR and induce the resistance to SST analogue (SSTA) treatment. A variant of SSTR5, sst5TMD4, has been found to disrupt SST signalling in breast cancer cells. In present study, we assayed the expression of sst5TMD4 in two non-transformed epithelial prostate cell lines (EPC): EPN, derived from a normal surrounding area of a prostate tumour, and CPEC, derived from the core of a prostate cancer tissue. In these cells, we evaluated the effects of SOM-230 (Novartis, Basilea, SW), a SSTA pan ligand with strong affinity for SSTR2 and 5. Cell cultures starved in red phenol-free DMEM and 1% charcoal treated FBS for 5 d were treated either with 10-6 SOM-230 or 10-8 SOM-230. After 24/48 h, cells were harvested for RT-PCR and for SDS–PAGE/western blot, or labelled with presidium iodide for cell cycle analysis by flow cytometer.
Results: SSTR2 and 5 were equally expressed in both cell lines. SSTR1 and 3, and sst5TMD4 mRNA levels were higher in CEPC than in EPN (P<0.001). In EPN, SOM 10-6 induced a significant caspase-dependent apoptosis, a reduction of S-phase proliferation together with an increase in bcl2 and a decrease in c-myc expression. In CPEC cells, SOM-230 treatment resulted in a modest apoptosis induction and a slight inhibition of cell growth, without changes of bcl-2 and c-myc levels.
Conclusions: sst5TMD4 variant is differently expressed in the EPC lines studied here. SOM-230 is effective in the control of cell growth in EPN cultures, while the reduced apoptotic response and the lack of growth arrest observed in CEPC could be due to presence of high levels of sst5TMD4 interfering with SST signalling.
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Endocrine Abstracts
ISSN 1470-3947 (print) | ISSN 1479-6848 (online)
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