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http://purl.uniprot.org/citations/19926313http://www.w3.org/1999/02/22-rdf-syntax-ns#typehttp://purl.uniprot.org/core/Journal_Citation
http://purl.uniprot.org/citations/19926313http://www.w3.org/2000/01/rdf-schema#comment"

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."xsd:string
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http://purl.uniprot.org/citations/19926313http://purl.uniprot.org/core/author"Abrahamsson P.A."xsd:string
http://purl.uniprot.org/citations/19926313http://purl.uniprot.org/core/author"Bjartell A."xsd:string
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http://purl.uniprot.org/citations/19926313http://purl.uniprot.org/core/date"2011"xsd:gYear
http://purl.uniprot.org/citations/19926313http://purl.uniprot.org/core/name"Urol Oncol"xsd:string
http://purl.uniprot.org/citations/19926313http://purl.uniprot.org/core/pages"436-445"xsd:string
http://purl.uniprot.org/citations/19926313http://purl.uniprot.org/core/title"Serotonin activates MAP kinase and PI3K/Akt signaling pathways in prostate cancer cell lines."xsd:string
http://purl.uniprot.org/citations/19926313http://purl.uniprot.org/core/volume"29"xsd:string
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