title: Sodium tungstate modulates ATM function upon DNA damage.
abstract: Both radiotherapy and most effective chemotherapeutic agents induce different types of DNA damage. Here we show that tungstate modulates cell response to DNA damaging agents. Cells treated with tungstate were more sensitive to etoposide, phleomycin and ionizing radiation (IR), all of which induce DNA double-strand breaks (DSBs). Tungstate also modulated the activation of the central DSB signalling kinase, ATM, in response to these agents. These effects required the functionality of the Mre11-Nbs1-Rad50 (MRN) complex and were mimicked by the inhibition of PP2A phosphatase. Therefore, tungstate may have adjuvant activity when combined with DNA-damaging agents in the treatment of several malignancies.
authors.affiliation: Institute for Research in Biomedicine, Barcelona, Spain.
authors.forename: C J
authors.initials: CJ
authors.lastname: Rodriguez-Hernandez
authors.forename: M
authors.initials: M
authors.lastname: Llorens-Agost
authors.forename: J
authors.initials: J
authors.lastname: Calbó
authors.forename: J R
authors.initials: JR
authors.lastname: Murguia
authors.forename: J J
authors.initials: JJ
authors.lastname: Guinovart
mesh_terms: D000818:Animals; D064007:Ataxia Telangiectasia Mutated Proteins; D018797:Cell Cycle Proteins / Q000378:metabolism / Q000502:physiology*; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D053903:DNA Breaks, Double-Stranded / Q000187:drug effects / Q000528:radiation effects; D004249:DNA Damage / Q000187:drug effects* / Q000235:genetics; D004268:DNA-Binding Proteins / Q000378:metabolism / Q000502:physiology*; D004305:Dose-Response Relationship, Drug; D004353:Drug Evaluation, Preclinical; D057809:HEK293 Cells; D006367:HeLa Cells; D006801:Humans; D051379:Mice; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism / Q000502:physiology*; D011829:Radiation Dosage; D011839:Radiation, Ionizing; D015398:Signal Transduction / Q000187:drug effects / Q000235:genetics / Q000528:radiation effects; D025521:Tumor Suppressor Proteins / Q000378:metabolism / Q000502:physiology*; D017973:Tungsten Compounds / Q000494:pharmacology*
chemical_list: D018797:Cell Cycle Proteins; D004268:DNA-Binding Proteins; D025521:Tumor Suppressor Proteins; D017973:Tungsten Compounds; C025399:sodium tungstate(VI); C576324:ATM protein, human; D064007:Ataxia Telangiectasia Mutated Proteins; C576325:Atm protein, mouse; D017346:Protein Serine-Threonine Kinases