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Article

Urotensin II receptor predicts the clinical outcome of prostate cancer patients and is involved in the regulation of motility of prostate adenocarcinoma cells

Paolo Grieco

Department of Pharmaceutical and Toxicological Chemistry, University of Naples Federico II, Naples, Italy

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Renato Franco

Pathology Unit, National Institute of Tumours, Fondazione “G. Pascale”, Naples, Italy

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Giuseppina Bozzuto

Department of Technology and Health, Italian National Institute of Health, Rome, Italy

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Laura Toccacieli

Department of Technology and Health, Italian National Institute of Health, Rome, Italy

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Alessandro Sgambato

Experimental Pharmacology Unit, National Institute of Tumours, Fondazione “G. Pascale”, Naples, Italy

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Monica Marra

Experimental Pharmacology Unit, National Institute of Tumours, Fondazione “G. Pascale”, Naples, Italy

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Silvia Zappavigna

Experimental Pharmacology Unit, National Institute of Tumours, Fondazione “G. Pascale”, Naples, Italy

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Mario Migaldi

Dipartimento di Laboratori, Anatomia Patologica e Medicina Legale, University of Modena and Reggio Emilia, Modena, Italy

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Giulio Rossi

Dipartimento di Laboratori, Anatomia Patologica e Medicina Legale, University of Modena and Reggio Emilia, Modena, Italy

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Stefano Striano

Uro‐Gynecological Department, National Institute of Tumours, Fondazione “G. Pascale”, Naples, Italy

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Luigi Marra

Uro‐Gynecological Department, National Institute of Tumours, Fondazione “G. Pascale”, Naples, Italy

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Luigi Gallo

Uro‐Gynecological Department, National Institute of Tumours, Fondazione “G. Pascale”, Naples, Italy

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Achille Cittadini

Institute of General Pathology, “Giovanni XXIII” Cancer Research Center, Catholic University of Sacred Heart, Rome, Italy

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Gerardo Botti

Pathology Unit, National Institute of Tumours, Fondazione “G. Pascale”, Naples, Italy

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Ettore Novellino

Department of Pharmaceutical and Toxicological Chemistry, University of Naples Federico II, Naples, Italy

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Agnese Molinari

Department of Technology and Health, Italian National Institute of Health, Rome, Italy

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Alfredo Budillon

Experimental Pharmacology Unit, National Institute of Tumours, Fondazione “G. Pascale”, Naples, Italy

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Michele Caraglia

Corresponding Author

E-mail address: [email protected]

Experimental Pharmacology Unit, National Institute of Tumours, Fondazione “G. Pascale”, Naples, Italy

Department of Biochemistry and Biophysics, Second University of Naples, Via Costantinopoli, 16 80138 Naples, Italy.
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First published: 15 November 2010
Cited by: 16

The authors declare no personal or financial conflict of interest.

Paolo Grieco and Renato Franco equally contributed to this study.

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. J. Cell. Biochem. 112: 341–353, 2011. © 2010 Wiley‐Liss, Inc.

Number of times cited according to CrossRef: 16

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