Serotonin activates MAP kinase and PI3K/Akt signaling pathways in prostate cancer cell lines

Nishtman Dizeyi, Petter Hedlund, Anders Bjartell, Martina Tinzl, Kristin Austild-Taskén, Per Anders Abrahamsson

Research output: Contribution to journalArticle

Abstract

Purpose: This study was conducted to examine the effects of 5-HT on extracellular signal-regulated kinase 1/2 (Erk1/2) and Akt pathways in prostate cancer (PC) cells. Methods: PC cell lines PC-3, Du145, and LNCaP stimulated with 5-HT in the presence of MEK or PI3K inhibitors and 5-HT receptor subtype 1A antagonist were analyzed by Western blotting and immunofluorescence. The proliferation assay BrdU and Boyden chamber were used to determine proliferation and migration, respectively. Results: 5-HT dose-dependently induced rapid activation of Erk1/2 in PC-3 and Du145 cells, whereas in LNCaP cells, Erk1/2 phosphorylation was slow and sustained for up to 18 h. Similarly, 5-HT induced phosphorylation of Akt within 1 hour of stimulation, however, Akt phosphorylation was more pronounced in Du145 cells compared with PC-3 or LNCaP cells. The action of 5-HT was inhibited to varying degrees by inhibitors of MAPK and PI3K as well as by a 5-HT receptor subtype 1A antagonist. In addition to proliferation, 5-HT induced migration of PC-3 and Du145 cells, which were alleviated by the aforementioned inhibitors. The effects of 5-HT on LNCaP cells appeared to be related to neuroendocrine-phenotype acquisition and chromogranin A and neuron specific enolase expression. Conclusions: This study addresses the role of 5-HT in Erk1/2 and Akt activation in PC cells. The data presented here identify 5-HT receptors as a novel target in castration-resistant PC. Furthermore, our observations are in line with previous studies, which point towards neuroendocrine factors facilitating progression and migration of prostatic cancer cells in an androgen-deficient environment. Nonetheless, additional studies are warranted to corroborate the role of 5-HTR antagonists as a potential target for anticancer therapy.

Original languageEnglish
Pages (from-to)436-445
Number of pages10
JournalUrologic Oncology: Seminars and Original Investigations
Volume29
Issue number4
DOIs
Publication statusPublished - Jul 2011

Keywords

  • 5-HT
  • 5-HTR antagonist
  • MAPK/Erk1/2
  • PI3K/Akt
  • Prostate cancer

ASJC Scopus subject areas

  • Oncology
  • Urology

Fingerprint Dive into the research topics of 'Serotonin activates MAP kinase and PI3K/Akt signaling pathways in prostate cancer cell lines'. Together they form a unique fingerprint.

  • Cite this