title: RETRACTED: Mitostatin is down-regulated in human prostate cancer and suppresses the invasive phenotype of prostate cancer cells.
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.
authors.affiliation: Department of Urology, Kimmel Cancer Center, Thomas Jefferson University, Philadelphia, Pennsylvania, United States of America.
authors.forename: Matteo
authors.initials: M
authors.lastname: Fassan
authors.forename: Domenico
authors.initials: D
authors.lastname: D'Arca
authors.forename: Juraj
authors.initials: J
authors.lastname: Letko
authors.forename: Andrea
authors.initials: A
authors.lastname: Vecchione
authors.forename: Marina P
authors.initials: MP
authors.lastname: Gardiman
authors.forename: Peter
authors.initials: P
authors.lastname: McCue
authors.forename: Bernadette
authors.initials: B
authors.lastname: Wildemore
authors.forename: Massimo
authors.initials: M
authors.lastname: Rugge
authors.forename: Dolores
authors.initials: D
authors.lastname: Shupp-Byrne
authors.forename: Leonard G
authors.initials: LG
authors.lastname: Gomella
authors.forename: Andrea
authors.initials: A
authors.lastname: Morrione
authors.forename: Renato V
authors.initials: RV
authors.lastname: Iozzo
authors.forename: Raffaele
authors.initials: R
authors.lastname: Baffa
mesh_terms: D000818:Animals; D002352:Carrier Proteins; D002448:Cell Adhesion; D045744:Cell Line, Tumor; D002465:Cell Movement; D049109:Cell Proliferation; D015536:Down-Regulation / Q000235:genetics*; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008297:Male; D051379:Mice; D008819:Mice, Nude; D009361:Neoplasm Invasiveness; D009367:Neoplasm Staging; D010641:Phenotype; D011471:Prostatic Neoplasms / Q000235:genetics* / Q000473:pathology*; D014410:Tumor Stem Cell Assay; D025521:Tumor Suppressor Proteins / Q000235:genetics* / Q000378:metabolism
chemical_list: D002352:Carrier Proteins; C502303:TCHP protein, human; D025521:Tumor Suppressor Proteins