title: Downregulation of protein tyrosine phosphatase PTPL1 alters cell cycle and upregulates invasion-related genes in prostate cancer cells.
abstract: PTPL1, a non-receptor type protein tyrosine phosphatase, has been involved in the regulation of apoptosis and invasiveness of various tumour cell types, but its role in prostate cancer remained to be investigated. We report here that downregulation of PTPL1 by small interfering RNA in PC3 cells decreases cell proliferation and concomitantly reduces the expression of cell cycle-related proteins such as cyclins E and B1, PCNA, PTTG1 and phospho-histone H3. PTPL1 downregulation also increases the invasion ability of PC3 cells through Matrigel coated membranes. cDNA array of PTPL1-silenced PC3 cells versus control cells showed an upregulation of invasion-related genes such as uPA, uPAR, tPA, PAI-1, integrin α6 and osteopontin. This increased expression was also confirmed in PTPL1-silenced DU145 prostate cancer cells by quantitative real time PCR and western blot. These findings suggest that PTPL1 is an important mediator of central cellular processes such as proliferation and invasion.
authors.affiliation: Instituto de Biomedicina de Sevilla, Hospital Universitario Virgen del Rocío/CSIC/Universidad de Sevilla, Avenida Manuel Siurot s/n, 41013 Seville, Spain.
authors.forename: Carolina
authors.initials: C
authors.lastname: Castilla
authors.forename: M Luz
authors.initials: ML
authors.lastname: Flores
authors.forename: José M
authors.initials: JM
authors.lastname: Conde
authors.forename: Rafael
authors.initials: R
authors.lastname: Medina
authors.forename: Francisco J
authors.initials: FJ
authors.lastname: Torrubia
authors.forename: Miguel A
authors.initials: MA
authors.lastname: Japón
authors.forename: Carmen
authors.initials: C
authors.lastname: Sáez
mesh_terms: D015153:Blotting, Western; D002453:Cell Cycle / Q000187:drug effects; D018797:Cell Cycle Proteins / Q000235:genetics; D049109:Cell Proliferation / Q000187:drug effects; D015536:Down-Regulation / Q000187:drug effects; D015971:Gene Expression Regulation, Enzymologic; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D039503:Integrin alpha6 / Q000235:genetics / Q000378:metabolism; D008297:Male; D009361:Neoplasm Invasiveness / Q000235:genetics; D053495:Osteopontin / Q000235:genetics / Q000378:metabolism; D010641:Phenotype; D017395:Plasminogen Activator Inhibitor 1 / Q000235:genetics / Q000378:metabolism; D011471:Prostatic Neoplasms / Q000201:enzymology / Q000235:genetics* / Q000473:pathology*; D054595:Protein Tyrosine Phosphatase, Non-Receptor Type 13 / Q000378:metabolism*; D034741:RNA, Small Interfering / Q000494:pharmacology; D060888:Real-Time Polymerase Chain Reaction; D055293:Receptors, Urokinase Plasminogen Activator / Q000235:genetics / Q000378:metabolism; D010959:Tissue Plasminogen Activator / Q000235:genetics / Q000378:metabolism; D014407:Tumor Cells, Cultured; D015854:Up-Regulation / Q000187:drug effects; D014568:Urokinase-Type Plasminogen Activator / Q000235:genetics / Q000378:metabolism
chemical_list: D018797:Cell Cycle Proteins; D039503:Integrin alpha6; D017395:Plasminogen Activator Inhibitor 1; D034741:RNA, Small Interfering; D055293:Receptors, Urokinase Plasminogen Activator; D053495:Osteopontin; C516742:PTPN13 protein, human; D054595:Protein Tyrosine Phosphatase, Non-Receptor Type 13; D010959:Tissue Plasminogen Activator; D014568:Urokinase-Type Plasminogen Activator