title: Activation of the Y1 receptor by neuropeptide Y regulates the growth of prostate cancer cells.
abstract: This study deals with the role of neuropeptide Y (NPY) in the regulation of cell proliferation. NPY is expressed in the normal and tumoral prostate, but no data on its possible role in prostate cancer (PCa) progression are available. Therefore, we evaluated the direct effect of NPY on the growth of the human PCa cell lines LNCaP (androgen dependent) and DU145 and PC3 (androgen independent). All PCa cell lines expressed Y1-R gene and protein. NPY treatment reduced the proliferation of LNCaP and DU145 cells and increased that of PC3 cells. The Y1-R antagonist BIBP3226 abolished such effects, suggesting a mandatory role of Y1-R in this process. LNCaP cells showed elevated constitutive levels of phosphorylated ERK1/2, which were not affected by NPY. In DU145 cells, NPY stimulated a long-lasting ERK1/2 activation, whereas, in PC3 cells, this effect was rapid and transient and required activation of protein kinase C. Moreover, in both cell lines, pretreatment with BIBP3226 prevented the NPY-induced ERK1/2 phosphorylation, further supporting Y1-R involvement. NPY treatment reduced forskolin-stimulated cAMP accumulation only in PC3 cells and did not change intracellular calcium concentration in any PCa cell line. These data indicate that NPY may directly regulate PCa cell growth via Y1-R. The direction of this effect appears to be related to the time kinetics of MAPK activation, i.e. long-lasting vs. transient, and to the clone-specific involvement of other intracellular signals. These findings suggest that NPY-related mechanisms might play a relevant role in the progression of PCa, at both androgen dependent and independent stages.
authors.affiliation: Istituto di Endocrinologia, via G. Balzaretti, 9-20133 Milano, Italy.
authors.forename: Massimiliano
authors.initials: M
authors.lastname: Ruscica
authors.forename: Elena
authors.initials: E
authors.lastname: Dozio
authors.forename: Stéphane
authors.initials: S
authors.lastname: Boghossian
authors.forename: Giorgio
authors.initials: G
authors.lastname: Bovo
authors.forename: Vera
authors.initials: V
authors.lastname: Martos Riaño
authors.forename: Marcella
authors.initials: M
authors.lastname: Motta
authors.forename: Paolo
authors.initials: P
authors.lastname: Magni
mesh_terms: D015153:Blotting, Western; D002118:Calcium / Q000378:metabolism; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D005576:Colforsin / Q000494:pharmacology; D000242:Cyclic AMP / Q000378:metabolism; D018450:Disease Progression; D004789:Enzyme Activation; D006801:Humans; D020935:MAP Kinase Signaling System; D008297:Male; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism; D048052:Mitogen-Activated Protein Kinase 3 / Q000378:metabolism; D009478:Neuropeptide Y / Q000378:metabolism*; D010766:Phosphorylation; D011471:Prostatic Neoplasms / Q000378:metabolism*; D011493:Protein Kinase C / Q000378:metabolism; D017476:Receptors, Neuropeptide Y / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction
chemical_list: D009478:Neuropeptide Y; D017476:Receptors, Neuropeptide Y; D005576:Colforsin; D000242:Cyclic AMP; D011493:Protein Kinase C; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; D002118:Calcium