title: Somatostatin, but not somatostatin receptor subtypes 2 and 5 selective agonists, inhibits calcitonin secretion and gene expression in the human medullary thyroid carcinoma cell line, TT.
abstract: Somatostatin (SRIH) analogs are commonly used to treat symptoms in medullary thyroid carcinoma (MTC), that expresses SRIH receptors (SSTR1 to SSTR5), as does the human MTC cell line TT. The aim of this work was to evaluate whether SRIH, SSTR2 and SSTR5-selective agonists influence calcitonin (CT) secretion and gene expression in the TT cell line. CT secretion was evaluated by chemiluminescence, and gene expression was analyzed by Northern blot. TT cell line proliferation was also assessed by [(3)H] thymidine ([(3)H]thy) incorporation and viable cell number count. SRIH significantly (p < 0.05) reduced [(3)H]thy incorporation (approx. 50 %), viable cell number (approx. 20 %), CT secretion (-30 %) and CT gene expression (approx. 2-fold). Exposure to the SSTR2-selective agonist, BIM-23 120, and to the SSTR5-selective agonist, BIM-23 206, did not modify CT secretion and mRNA levels in TT cells. Thus, SRIH inhibits DNA synthesis, cell proliferation, CT secretion and CT gene expression in the TT cell line, while SSTR2 and 5 selective agonists, although influencing DNA synthesis and cell proliferation, do not modify CT gene expression, suggesting that SRIH may influence gene expression acting through SSTRs other than subtypes 2 and 5. Furthermore, these findings may explain the erratic response of MTC patients in terms of CT plasma levels to treatment with SRIH analogs, like octreotide and lanreotide, which interact mainly with SSTR2 and 5.
authors.affiliation: Section of Endocrinology, Department of Biomedical Sciences and Advanced Therapies, University of Ferrara, Via Savonarola 9, 44100 Ferrara, Italy.
authors.forename: M C
authors.initials: MC
authors.lastname: Zatelli
authors.forename: F
authors.initials: F
authors.lastname: Tagliati
authors.forename: J E
authors.initials: JE
authors.lastname: Taylor
authors.forename: D
authors.initials: D
authors.lastname: Piccin
authors.forename: M D
authors.initials: MD
authors.lastname: Culler
authors.forename: E C
authors.initials: EC
authors.lastname: degli Uberti
mesh_terms: D015152:Blotting, Northern; D002116:Calcitonin / Q000037:antagonists & inhibitors / Q000096:biosynthesis* / Q000235:genetics*; D002452:Cell Count; D002455:Cell Division / Q000187:drug effects; D004247:DNA / Q000096:biosynthesis / Q000235:genetics; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects*; D006801:Humans; D017481:Receptors, Somatostatin / Q000819:agonists*; D013004:Somatostatin / Q000378:metabolism* / Q000494:pharmacology; D013964:Thyroid Neoplasms / Q000235:genetics* / Q000378:metabolism*; D014407:Tumor Cells, Cultured
chemical_list: D017481:Receptors, Somatostatin; D013004:Somatostatin; C094573:somatostatin receptor 5; D002116:Calcitonin; D004247:DNA; C093733:somatostatin receptor 2