title: Stable suppression of tumorigenicity by Pin1-targeted RNA interference in prostate cancer.
abstract: OBJECTIVE
  The peptidyl-prolyl isomrase Pin1 plays a catalytic role in oncogenesis in solid cancers, including prostate cancer. In the present study, we sought to determine the potential of Pin1-targeted gene silencing in inhibiting cellular growth and tumorigenicity in prostate cancer.
  
  
  METHODS
  A retrovirus-mediated RNA interference targeting Pin1 was expressed in PC3 and LNCaP cells, and cell growth and several transformed properties were investigated.
  
  
  RESULTS
  The stable expression of Pin1-specific small interfering RNA constructs in PC3 and LNCaP cells significantly reduced cellular proliferation, colony formation, migration, and invasion but strongly enhanced the apoptotic response induced by serum depletion or treatment with anticancer agents. Furthermore, Pin1 depletion significantly suppressed tumorigenic potential in athymic mice, resulting in the inhibition of both tumor growth and angiogeneisis.
  
  
  CONCLUSIONS
  These results strongly suggest that Pin1 plays an important role not only in tumorigenesis but also in the maintenance of the transformed phenotype in prostate cancer cells. Hence, Pin1 may serve as a promising therapeutic target, particularly for recurrent prostate tumors.
authors.affiliation: Department of Pathology, Yokohama City University School of Medicine, Yokohama, Japan. aryo@yokohama-cu.ac.jp
authors.forename: Akihide
authors.initials: A
authors.lastname: Ryo
authors.forename: Hiroji
authors.initials: H
authors.lastname: Uemura
authors.forename: Hitoshi
authors.initials: H
authors.lastname: Ishiguro
authors.forename: Tatsuya
authors.initials: T
authors.lastname: Saitoh
authors.forename: Akira
authors.initials: A
authors.lastname: Yamaguchi
authors.forename: Kilian
authors.initials: K
authors.lastname: Perrem
authors.forename: Yoshinobu
authors.initials: Y
authors.lastname: Kubota
authors.forename: Kun Ping
authors.initials: KP
authors.lastname: Lu
authors.forename: Ichiro
authors.initials: I
authors.lastname: Aoki
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects; D015153:Blotting, Western; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D016895:Culture Media, Serum-Free / Q000494:pharmacology; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D000072340:NIMA-Interacting Peptidylprolyl Isomerase; D009389:Neovascularization, Pathologic / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D019696:Peptidylprolyl Isomerase / Q000235:genetics*; D011471:Prostatic Neoplasms / Q000235:genetics / Q000473:pathology*; D034622:RNA Interference / Q000502:physiology*; D034741:RNA, Small Interfering / Q000235:genetics; D013997:Time Factors; D042461:Vascular Endothelial Growth Factor A / Q000032:analysis; D042582:Vascular Endothelial Growth Factor C / Q000032:analysis; D023041:Xenograft Model Antitumor Assays / Q000379:methods
chemical_list: D000970:Antineoplastic Agents; D016895:Culture Media, Serum-Free; D000072340:NIMA-Interacting Peptidylprolyl Isomerase; D034741:RNA, Small Interfering; D042461:Vascular Endothelial Growth Factor A; D042582:Vascular Endothelial Growth Factor C; C000606846:PIN1 protein, human; D019696:Peptidylprolyl Isomerase; C000606850:Pin1 protein, mouse