Expression of serotonin receptors 2B and 4 in human prostate cancer tissue and effects of their antagonists on prostate cancer cell lines
Expression of serotonin receptors 2B and 4 in human prostate cancer tissue and effects of their antagonists on prostate cancer cell lines
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DOI：
10.1016/j.eururo.2005.02.006
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发表时间：
2005-06-01
期刊：
影响因子：
23.4
通讯作者：
Abrahamsson, PA
中科院分区：
文献类型：
--
作者：
Dizeyi, N;Bjartell, A;Abrahamsson, PA
目的：神经内分泌 (NE) 细胞产物受体的过度表达被认为有助于激素难治性前列腺癌 (HRPC) 的发展。在本研究中，我们评估了HRPC中5-HTR2B和5-HTR4的表达，以及它们的拮抗剂对PC细胞系生长的影响。方法：通过免疫组化、蛋白质印迹和RT-PCR测定蛋白质和mRNA的表达。使用 ELISA-BrdU 增殖测定体外测定 PC 细胞系的生长抑制，并通过流式细胞术评估细胞周期。结果：在低级别和高级肿瘤、PIN 和 BPH 细胞以及血管内皮细胞中观察到 5-HTR2B 的免疫染色，而 5-HTR4 主要在高级肿瘤中发现。该结果通过蛋白质印迹分析得到证实。在mRNA水平，5-HTR4 mRNA在DU145和LNCaP细胞中表达。两种受体亚型的拮抗剂以剂量依赖性方式抑制PC细胞的增殖。结论：本结果表明5-HTR存在于不同的肿瘤阶段，并且这些受体的拮抗剂可以抑制雄激素非依赖性PC细胞系的增殖活性。 (c) 2005 Elsevier B.V 保留所有权利。
Objectives: Overexpression of receptors to neuroendocrine (NE) cell products has been suggested to contribute to development of hormone-refractory prostate cancer (HRPC). In this study, we evaluated the expression of 5-HTR2B and 5-HTR4 in HRPC, and the effects of their antagonist on PC cell line growth.Methods: Proteins and mRNA expression was determined by immunohistochemistry, western blot and RT-PCR. Growth inhibition of PC cell lines was determined in vitro using ELISA-BrdU proliferation assay and cell cycle was evaluated by flow cytometry.Results: Immunostaining of 5-HTR2B was observed in low-grade and high-grade tumours, PIN and BPH cells, and in vascular endothelial cells, whereas 5-HTR4 was found predominantly in high-grade tumours. This result was confirmed by western blot analysis. At the mRNA level, 5-HTR4 mRNA was expressed in DU145 and LNCaP cells. Antagonists to both receptor subtypes inhibited proliferation of PC cells in a dose-dependent manner.Conclusions: The present result indicate that 5-HTRs are present at various tumour stages and that antagonists to these receptors can inhibit the proliferative activity of androgen-independent PC cell lines. (c) 2005 Elsevier B.V All rights reserved.