کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
2197023 1550949 2010 9 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Regulation of prostate cancer cell proliferation by somatostatin receptor activation
موضوعات مرتبط
علوم زیستی و بیوفناوری بیوشیمی، ژنتیک و زیست شناسی مولکولی بیولوژی سلول
پیش نمایش صفحه اول مقاله
Regulation of prostate cancer cell proliferation by somatostatin receptor activation
چکیده انگلیسی

Although some evidence supports the antitumoral effects of somatostatin (SRIF) and related agonists, the available data in prostate cancer (PCa) model systems and clinical studies are few, conflicting and not conclusive. This study investigated the effects of lanreotide and new mono- and bi-specific SRIF agonists on proliferation, ligand-driven SRIF receptor (sst) dimerization and secretory pattern of the IGF system in LNCaP cells, a model of androgen-dependent PCa. LNCaP expressed all ssts, but sst4. Among them, sst1 and sst3 were inversely regulated by serum concentration. sst1/sst2 and sst2/sst5 dimers were constitutively present and further stabilized by treatment with BIM-23704 (sst1/sst2) and BIM-23244 (sst2/sst5), respectively. Dose-response studies showed that lanreotide and BIM-23244 were significantly more potent in inhibiting LNCaP cell proliferation than BIM-23120 (sst2) and BIM-23206 (sst5) alone or in combination. Treatment with BIM-23296 (sst1) markedly reduced cell proliferation, whereas exposure to BIM-23704 resulted in a lower cell growth inhibition. The antiproliferative effects of BIM-23244, lanreotide and BIM-23704 were unchanged, reduced and abolished by the sst2 antagonist BIM-23627, respectively. All SRIF analogs caused a significant induction in p27KipI and p21 and down-regulation of protein expression of cyclin E, as well as reduced IGF-I and IGF-II secretion. In particular, the administration of exogenous IGF-I, at variance to IGF-II, counteracted the inhibitory effect on cell proliferation of these compounds. Moreover, SRIF agonists reduced endogenous IGFBP-3 proteolysis. These results show that, in LNCaP cells, activation of sst1 and sst2/sst5 results in relevant antiproliferative/antisecretive actions.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Molecular and Cellular Endocrinology - Volume 315, Issues 1–2, 5 February 2010, Pages 254–262
نویسندگان
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