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Serotonin activates MAP kinase and PI3K/Akt signaling pathways in prostate cancer cell lines
Malmö University Hospital, Lund University, Malmö.
Linköping University, Department of Medical and Health Sciences, Clinical Pharmacology. Linköping University, Faculty of Health Sciences.
Malmö University Hospital, Lund University, Malmö.
Malmö University Hospital, Lund University, Malmö.
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2011 (English)In: Urologic Oncology, ISSN 1078-1439, E-ISSN 1873-2496, Vol. 29, no 4, 436-445 p.Article in journal (Refereed) Published
Abstract [en]

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.

Place, publisher, year, edition, pages
Elsevier, 2011. Vol. 29, no 4, 436-445 p.
Keyword [en]
Prostate cancer; 5-HT; 5-HTR antagonist; MAPK/Erk1/2; PI3K/Akt
National Category
Medical and Health Sciences
URN: urn:nbn:se:liu:diva-77376DOI: 10.1016/j.urolonc.2009.09.013PubMedID: 19926313OAI: diva2:526563
Available from: 2012-05-14 Created: 2012-05-14 Last updated: 2012-05-24

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Hedlund, Petter
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