Matteo Fassan, Department of Urology, Kimmel Cancer Center, Thomas Jefferson University, Philadelphia, Pennsylvania; Department of Diagnostic Medicine and Special Therapies, University of Padova, Padova, ItalyFollow
Domenico D'Arca, Department of Urology, Kimmel Cancer Center, Thomas Jefferson University, Philadelphia, Pennsylvania
Juraj Letko, Department of Urology, Kimmel Cancer Center, Thomas Jefferson University, Philadelphia, Pennsylvania
Andrea Vecchione, Department of Urology, Kimmel Cancer Center, Thomas Jefferson University, Philadelphia, Pennsylvania; Division of Pathology, II Faculty of Medicine, University ‘‘La Sapienza,’’ Ospedale Sant’Andrea, Rome, ItalyFollow
Marina P Gardiman, Department of Diagnostic Medicine and Special Therapies, University of Padova, Padova, ItalyFollow
Peter McCue, Department of Pathology, Anatomy and Cell Biology, Kimmel Cancer Center, Thomas Jefferson University, Philadelphia, PennsylvaniaFollow
Bernadette Wildemore, Department of Pathology, Anatomy and Cell Biology, Kimmel Cancer Center, Thomas Jefferson University, Philadelphia, Pennsylvania
Massimo Rugge, Department of Diagnostic Medicine and Special Therapies, University of Padova, Padova, ItalyFollow
Dolores Shupp-Byrne, Department of Urology, Kimmel Cancer Center, Thomas Jefferson University, Philadelphia, PennsylvaniaFollow
Leonard G Gomella, Department of Urology, Kimmel Cancer Center, Thomas Jefferson University, Philadelphia, PennsylvaniaFollow
Andrea Morrione, Department of Urology, Kimmel Cancer Center, Thomas Jefferson University, Philadelphia, PennsylvaniaFollow
Renato V Iozzo, Department of Pathology, Anatomy and Cell Biology, Kimmel Cancer Center, Thomas Jefferson University, Philadelphia, PennsylvaniaFollow
Raffaele Baffa, Department of Urology, Kimmel Cancer Center, Thomas Jefferson University, Philadelphia, PennsylvaniaFollow

Document Type

Article

Publication Date

5-1-2011

Comments

This article has been peer reviewed and is published in PLoS One 2011, 6(5). The published version is available at DOI: doi:10.1371/journal.pone.0019771. © Public Library of Science

Abstract

MITOSTATIN, a novel putative tumor suppressor gene induced by decorin overexpression, is expressed in most normal human tissues but is markedly down-regulated in advanced stages of mammary and bladder carcinomas. Mitostatin negatively affects cell growth, induces cell death and regulates the expression and activation levels of Hsp27. In this study, we demonstrated that ectopic expression of Mitostatin in PC3, DU145, and LNCaP prostate cancer cells not only induced a significant reduction in cell growth, but also inhibited migration and invasion. Moreover, Mitostatin inhibited colony formation in soft-agar of PC3 and LNCaP cells as well as tumorigenicity of LNCaP cells in nude mice. Conversely, targeting endogenous Mitostatin by siRNA and anti-sense strategies in PC3 and DU145 prostate cancer cells enhanced the malignant phenotype in both cell lines. In agreement of these anti-oncogenic roles, we discovered that Mitostatin was absent in ∼35% (n = 124) of prostate tumor samples and its overall reduction was associated with advanced cancer stages. Collectively, our findings indicate that MITOSTATIN may acts as a tumor suppressor gene in prostate cancer and provide a novel cellular and molecular mechanism to be further exploited and deciphered in our understanding of prostate cancer progression.

PubMed ID

21573075

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