title: Altered RECQL5 expression in urothelial bladder carcinoma increases cellular proliferation and makes RECQL5 helicase activity a novel target for chemotherapy.
abstract: RECQ helicases are a family of enzymes with both over lapping and unique functions. Functional autosomal recessive loss of three members of the family BLM, WRN and RECQL4, results in hereditary human syndromes characterized by cancer predisposition and premature aging, but despite the finding that RECQL5 deficient mice are cancer prone, no such link has been made to human RECQL5. Here we demonstrate that human urothelial carcinoma of the bladder (UCC) has increased expression of RECQL5 compared to normal bladder tissue and that increasing RECQL5 expression can drive proliferation of normal bladder cells and is associated with poor prognosis. Further, by expressing a helicase dead RECQL5 and by depleting bladder cancer cells of RECQL5 we show that inhibition of RECQL5 activity has potential as a new target for treatment of UCC.
authors.affiliation: Academic Unit of Molecular Oncology, Sheffield Institute for Nucleic Acids (SInFoNiA), Department of Oncology and Metabolism, University of Sheffield, Sheffield S10 2RX, United Kingdom.
authors.forename: Karl
authors.initials: K
authors.lastname: Patterson
authors.affiliation: Academic Unit of Molecular Oncology, Sheffield Institute for Nucleic Acids (SInFoNiA), Department of Oncology and Metabolism, University of Sheffield, Sheffield S10 2RX, United Kingdom.
authors.forename: Lovleen
authors.initials: L
authors.lastname: Arya
authors.affiliation: Academic Unit of Molecular Oncology, Sheffield Institute for Nucleic Acids (SInFoNiA), Department of Oncology and Metabolism, University of Sheffield, Sheffield S10 2RX, United Kingdom.
authors.forename: Sarah
authors.initials: S
authors.lastname: Bottomley
authors.affiliation: Academic Unit of Urology, Sheffield Institute for Nucleic Acids (SInFoNiA), Department of Oncology and Metabolism, University of Sheffield, Sheffield S10 2RX, United Kingdom.
authors.forename: Susan
authors.initials: S
authors.lastname: Morgan
authors.affiliation: Academic Unit of Molecular Oncology, Sheffield Institute for Nucleic Acids (SInFoNiA), Department of Oncology and Metabolism, University of Sheffield, Sheffield S10 2RX, United Kingdom.
authors.forename: Angela
authors.initials: A
authors.lastname: Cox
authors.affiliation: Academic Unit of Urology, Sheffield Institute for Nucleic Acids (SInFoNiA), Department of Oncology and Metabolism, University of Sheffield, Sheffield S10 2RX, United Kingdom.
authors.forename: James
authors.initials: J
authors.lastname: Catto
authors.affiliation: Academic Unit of Molecular Oncology, Sheffield Institute for Nucleic Acids (SInFoNiA), Department of Oncology and Metabolism, University of Sheffield, Sheffield S10 2RX, United Kingdom.
authors.forename: Helen E
authors.initials: HE
authors.lastname: Bryant
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology; D002295:Carcinoma, Transitional Cell / Q000188:drug therapy / Q000235:genetics* / Q000378:metabolism* / Q000473:pathology; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D002470:Cell Survival / Q000235:genetics; D018450:Disease Progression; D004789:Enzyme Activation; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D011379:Prognosis; D053484:RecQ Helicases / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000378:metabolism*; D013312:Stress, Physiological; D016019:Survival Analysis; D001749:Urinary Bladder Neoplasms / Q000188:drug therapy / Q000235:genetics* / Q000378:metabolism* / Q000473:pathology
chemical_list: D000970:Antineoplastic Agents; C506732:RECQL5 protein, human; D053484:RecQ Helicases
keywords: RECQL5; bladder cancer; helicase; targeted therapy