1. Expression of serotonin receptors 2B and 4 in human prostate cancer tissue and effects of their antagonists on prostate cancer cell lines.
- Author
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Dizeyi N, Bjartell A, Hedlund P, Taskén KA, Gadaleanu V, and Abrahamsson PA
- Subjects
- Biomarkers, Tumor, Blotting, Western, Cell Line, Tumor drug effects, Cell Line, Tumor metabolism, Cell Proliferation drug effects, Enzyme-Linked Immunosorbent Assay, Flow Cytometry, Humans, Immunohistochemistry, In Vitro Techniques, Male, RNA, Messenger biosynthesis, RNA, Messenger genetics, Receptor, Serotonin, 5-HT2B genetics, Receptors, Serotonin, 5-HT4 genetics, Reverse Transcriptase Polymerase Chain Reaction, Serotonin 5-HT2 Receptor Antagonists, Serotonin 5-HT4 Receptor Antagonists, Prostatic Neoplasms drug therapy, Prostatic Neoplasms metabolism, Prostatic Neoplasms pathology, Receptor, Serotonin, 5-HT2B biosynthesis, Receptors, Serotonin, 5-HT4 biosynthesis, Serotonin Antagonists pharmacology
- Abstract
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.
- Published
- 2005
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