title: Urotensin II receptor predicts the clinical outcome of prostate cancer patients and is involved in the regulation of motility of prostate adenocarcinoma cells.
abstract: Urotensin II (UT-II) is a potent vasoconstrictor peptide and its receptor (UTR) was correlated with human cortico-adrenal carcinoma proliferation. In this study, we have evaluated the correlation between UTR expression and prognosis of human prostate adenocarcinoma and the involvement of this receptor in the regulation of biological properties on both in vivo and in vitro models. UTR mRNA and protein, evaluated by real-time PCR and Western blotting, respectively, were expressed at high levels only in androgen-dependent LNCaP cells. In order to investigate UTR changes occurring in human prostate tumorigenesis, we have also evaluated the expression of UTR in vivo in 195 human prostate tissue samples. UTR was always expressed at low intensity in hyperplastic tissues and at high intensity in well-differentiated carcinomas (Gleason 2-3). Moreover, we have evaluated the effects of an antagonist of UTR, urantide on migration and invasion of LNCaP cells. Urantide induced a dose-dependent decrease of motility and invasion of LNCaP cells whose characteristic ameboid movement seems to be advantageous for their malignancy. These effects were paralleled by down-regulating the autophosphorylation of focal adhesion kinase and the integrin surface expression on LNCaP cells. The effects on cell motility and invasion were likely due to the inhibition of RhoA activity induced by both urantide and shRNA UTR. These data suggest that UTR can be considered a prognostic marker in human prostate adenocarcinoma patients.
authors.affiliation: Department of Pharmaceutical and Toxicological Chemistry, University of Naples Federico II, Naples, Italy.
authors.forename: Paolo
authors.initials: P
authors.lastname: Grieco
authors.forename: Renato
authors.initials: R
authors.lastname: Franco
authors.forename: Giuseppina
authors.initials: G
authors.lastname: Bozzuto
authors.forename: Laura
authors.initials: L
authors.lastname: Toccacieli
authors.forename: Alessandro
authors.initials: A
authors.lastname: Sgambato
authors.forename: Monica
authors.initials: M
authors.lastname: Marra
authors.forename: Silvia
authors.initials: S
authors.lastname: Zappavigna
authors.forename: Mario
authors.initials: M
authors.lastname: Migaldi
authors.forename: Giulio
authors.initials: G
authors.lastname: Rossi
authors.forename: Stefano
authors.initials: S
authors.lastname: Striano
authors.forename: Luigi
authors.initials: L
authors.lastname: Marra
authors.forename: Luigi
authors.initials: L
authors.lastname: Gallo
authors.forename: Achille
authors.initials: A
authors.lastname: Cittadini
authors.forename: Gerardo
authors.initials: G
authors.lastname: Botti
authors.forename: Ettore
authors.initials: E
authors.lastname: Novellino
authors.forename: Agnese
authors.initials: A
authors.lastname: Molinari
authors.forename: Alfredo
authors.initials: A
authors.lastname: Budillon
authors.forename: Michele
authors.initials: M
authors.lastname: Caraglia
mesh_terms: D000230:Adenocarcinoma / Q000175:diagnosis* / Q000235:genetics / Q000378:metabolism; D014408:Biomarkers, Tumor / Q000235:genetics / Q000378:metabolism*; D002465:Cell Movement; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008297:Male; D011471:Prostatic Neoplasms / Q000175:diagnosis* / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D043562:Receptors, G-Protein-Coupled / Q000235:genetics / Q000378:metabolism*; D016896:Treatment Outcome; D014407:Tumor Cells, Cultured
chemical_list: D014408:Biomarkers, Tumor; D012333:RNA, Messenger; D043562:Receptors, G-Protein-Coupled; C121697:UTS2R protein, human