TY - JOUR
T1 - Mitostatin is down-regulated in human prostate cancer and suppresses the invasive phenotype of prostate cancer cells
AU - Fassan, Matteo
AU - D'Arca, Domenico
AU - Letko, Juraj
AU - Vecchione, Andrea
AU - Gardiman, Marina P.
AU - McCue, Peter
AU - Wildemore, Bernadette
AU - Rugge, Massimo
AU - Shupp-Byrne, Dolores
AU - Gomella, Leonard G.
AU - Morrione, Andrea
AU - Iozzo, Renato V.
AU - Baffa, Raffaele
PY - 2011
Y1 - 2011
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=79955812386&partnerID=8YFLogxK
U2 - 10.1371/journal.pone.0019771
DO - 10.1371/journal.pone.0019771
M3 - Article
C2 - 21573075
AN - SCOPUS:79955812386
SN - 1932-6203
VL - 6
JO - PLoS ONE
JF - PLoS ONE
IS - 5
M1 - e19771
ER -