title: Overexpression of the prolyl isomerase PIN1 promotes cell growth in             osteosarcoma cells.
abstract: PIN1 was recently identified as a peptidyl-prolyl cis-trans isomerase (PPIase).             It binds to and isomerizes specific pSer/Thr-Pro motifs and catalytically induces             conformational changes after phosphorylation. PIN1 plays an important role in             several cellular events, such as cell cycle progression, transcriptional regulation,             RNA processing, cell proliferation and differentiation. The relationship between             PIN1 and osteosarcoma has not been previously studied. In the present study, we             investigated the expression pattern of PIN1 in human osteosarcoma tissues and             the role of PIN1 in osteosarcoma generation and development. The expression levels             of PIN1 were detected by immunohistochemistry and western blotting. Results demonstrated             that the expression of PIN1, cyclin D1 and β-catenin were significantly higher             in human osteosarcoma tissues compared to normal tissues. The in vitro effects             of PIN1 overexpression were studied in human osteosarcoma cell lines. Adenovirus-mediated             PIN1 overexpression significantly stimulated the proliferation of MG-63 and U2-OS             osteosarcoma cells by 148±10.5 and 187±21.5%, respectively. In FACS analysis,             U2-OS cells displayed significant levels of arrest in cell cycle progression at             the G0/G1 phase. Consistent with increased cell growth, levels of cyclin D1 and             cyclin E and their associated cyclin-dependent kinases, CDK4 and CDK6, were enhanced             in PIN1-overexpressed cells compared with the control virus-transfected cells.             When the PIN1 inhibitor juglone was added to the cells, the proliferative effects             of PIN1 were abolished. These results suggest that PIN1 may play an important             role in tumorigenesis and tumor progression of osteosarcoma and therefore, provide             a new target for gene therapy.
authors.affiliation: Department of Orthopaedic Surgery, Chonbuk National University Medical School, Jeonju, Jeonbuk 561-756, Republic of Korea.
authors.forename: Lu
authors.initials: L
authors.lastname: Zhou
authors.forename: Byung-Hyun
authors.initials: BH
authors.lastname: Park
authors.forename: Jong Hyuk
authors.initials: JH
authors.lastname: Park
authors.forename: Kyu Yun
authors.initials: KY
authors.lastname: Jang
authors.forename: Ho Sung
authors.initials: HS
authors.lastname: Park
authors.forename: Sajeev
authors.initials: S
authors.lastname: Wagle
authors.forename: Kwang-Bok
authors.initials: KB
authors.lastname: Lee
authors.forename: Jung Ryul
authors.initials: JR
authors.lastname: Kim
mesh_terms: D015153:Blotting, Western; D001859:Bone Neoplasms / Q000378:metabolism / Q000473:pathology*; D001842:Bone and Bones / Q000378:metabolism / Q000473:pathology*; D002453:Cell Cycle; D049109:Cell Proliferation; D018844:Cyclin-Dependent Kinases / Q000378:metabolism; D016213:Cyclins / Q000378:metabolism; D006801:Humans; D007124:Immunoenzyme Techniques; D000072340:NIMA-Interacting Peptidylprolyl Isomerase; D012516:Osteosarcoma / Q000378:metabolism / Q000473:pathology*; D019696:Peptidylprolyl Isomerase / Q000378:metabolism*; D014407:Tumor Cells, Cultured
chemical_list: D016213:Cyclins; D000072340:NIMA-Interacting Peptidylprolyl Isomerase; D018844:Cyclin-Dependent Kinases; C000606846:PIN1 protein, human; D019696:Peptidylprolyl Isomerase