Serotonin activates MAP kinase and PI3K/Akt signaling pathways in prostate cancer cell lines
2011 (English)In: Urologic Oncology, ISSN 1078-1439, E-ISSN 1873-2496, Vol. 29, no 4, 436-445 p.Article in journal (Refereed) Published
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.
Prostate cancer; 5-HT; 5-HTR antagonist; MAPK/Erk1/2; PI3K/Akt
Medical and Health Sciences
IdentifiersURN: urn:nbn:se:liu:diva-77376DOI: 10.1016/j.urolonc.2009.09.013PubMedID: 19926313OAI: oai:DiVA.org:liu-77376DiVA: diva2:526563