Expression of serotonin receptors 2B and 4 in human prostate cancer tissue and effects of their antagonists on prostate cancer cell lines

Eur Urol. 2005 Jun;47(6):895-900. doi: 10.1016/j.eururo.2005.02.006. Epub 2005 Mar 3.


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.

Publication types

  • Comparative Study

MeSH terms

  • 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
  • Prostatic Neoplasms* / drug therapy
  • Prostatic Neoplasms* / metabolism
  • Prostatic Neoplasms* / pathology
  • RNA, Messenger / biosynthesis
  • RNA, Messenger / genetics
  • Receptor, Serotonin, 5-HT2B / biosynthesis*
  • Receptor, Serotonin, 5-HT2B / genetics
  • Receptors, Serotonin, 5-HT4 / biosynthesis*
  • Receptors, Serotonin, 5-HT4 / genetics
  • Reverse Transcriptase Polymerase Chain Reaction
  • Serotonin 5-HT2 Receptor Antagonists
  • Serotonin 5-HT4 Receptor Antagonists
  • Serotonin Antagonists / pharmacology*


  • Biomarkers, Tumor
  • RNA, Messenger
  • Receptor, Serotonin, 5-HT2B
  • Serotonin 5-HT2 Receptor Antagonists
  • Serotonin 5-HT4 Receptor Antagonists
  • Serotonin Antagonists
  • Receptors, Serotonin, 5-HT4