title: Expression of serotonin receptors 2B and 4 in human prostate cancer tissue and effects of their antagonists on prostate cancer cell lines.
abstract: OBJECTIVE
  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.
authors.affiliation: Department of Urology, Malmö University Hospital, Lund University; SE-205 02 Malmö, Sweden. nishtman.dizeyi@kir.mas.lu.se
authors.forename: N
authors.initials: N
authors.lastname: Dizeyi
authors.forename: A
authors.initials: A
authors.lastname: Bjartell
authors.forename: P
authors.initials: P
authors.lastname: Hedlund
authors.forename: K A
authors.initials: KA
authors.lastname: Taskén
authors.forename: V
authors.initials: V
authors.lastname: Gadaleanu
authors.forename: P-A
authors.initials: PA
authors.lastname: Abrahamsson
mesh_terms: D014408:Biomarkers, Tumor; D015153:Blotting, Western; D045744:Cell Line, Tumor / Q000187:drug effects / Q000378:metabolism; D049109:Cell Proliferation / Q000187:drug effects; D004797:Enzyme-Linked Immunosorbent Assay; D005434:Flow Cytometry; D006801:Humans; D007150:Immunohistochemistry; D066298:In Vitro Techniques; D008297:Male; D011471:Prostatic Neoplasms / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D044403:Receptor, Serotonin, 5-HT2B / Q000096:biosynthesis* / Q000235:genetics; D044422:Receptors, Serotonin, 5-HT4 / Q000096:biosynthesis* / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D058830:Serotonin 5-HT2 Receptor Antagonists; D058832:Serotonin 5-HT4 Receptor Antagonists; D012702:Serotonin Antagonists / Q000494:pharmacology*
chemical_list: D014408:Biomarkers, Tumor; D012333:RNA, Messenger; D044403:Receptor, Serotonin, 5-HT2B; D058830:Serotonin 5-HT2 Receptor Antagonists; D058832:Serotonin 5-HT4 Receptor Antagonists; D012702:Serotonin Antagonists; D044422:Receptors, Serotonin, 5-HT4