title: The repair capacity of lung cancer cell lines A549 and H1299 depends on HMGB1 expression level and the p53 status.
abstract: Elucidation of the cellular components responsive to chemotherapeutic agents as cisplatin rationalizes the strategy for anticancer chemotherapy. The removal of the cisplatin/DNA lesions gives the chance to the cancer cells to survive and compromises the chemotherapeutical treatment. Therefore, the cell repair efficiency is substantial for the clinical outcome. High mobility group box 1 (HMGB1) protein is considered to be involved in the removal of the lesions as it binds with high affinity to cisplatin/DNA adducts. We demonstrated that overexpression of HMGB1 protein inhibited cis-platinated DNA repair in vivo and the effect strongly depended on its C-terminus. We registered increased levels of DNA repair after HMGB1 silencing only in p53 defective H1299 lung cancer cells. Next, introduction of functional p53 resulted in DNA repair inhibition. H1299 cells overexpressing HMGB1 were significantly sensitized to treatment with cisplatin demonstrating the close relation between the role of HMGB1 in repair of cis-platinated DNA and the efficiency of the anticancer drug, the process being modulated by the C-terminus. In A549 cells with functional p53, the repair of cisplatin/DNA adducts is determined by а complex action of HMGB1 and p53 as an increase of DNA repair capacity was registered only after silencing of both proteins.
authors.affiliation: Institute of Molecular Biology "Roumen Tsanev," Bulgarian Academy of Sciences, Akad. G.Bonchev Street, Bl. 21, 1113 Sofia, Bulgaria.
authors.forename: Shazie
authors.initials: S
authors.lastname: Yusein-Myashkova
authors.affiliation: Institute of Molecular Biology "Roumen Tsanev," Bulgarian Academy of Sciences, Akad. G.Bonchev Street, Bl. 21, 1113 Sofia, Bulgaria.
authors.forename: Ivan
authors.initials: I
authors.lastname: Stoykov
authors.affiliation: Institute of Molecular Biology "Roumen Tsanev," Bulgarian Academy of Sciences, Akad. G.Bonchev Street, Bl. 21, 1113 Sofia, Bulgaria.
authors.forename: Anastas
authors.initials: A
authors.lastname: Gospodinov
authors.affiliation: Institute of Molecular Biology "Roumen Tsanev," Bulgarian Academy of Sciences, Akad. G.Bonchev Street, Bl. 21, 1113 Sofia, Bulgaria.
authors.forename: Iva
authors.initials: I
authors.lastname: Ugrinova
authors.affiliation: Institute of Molecular Biology "Roumen Tsanev," Bulgarian Academy of Sciences, Akad. G.Bonchev Street, Bl. 21, 1113 Sofia, Bulgaria eva@bio21.bas.bg.
authors.forename: Evdokia
authors.initials: E
authors.lastname: Pasheva
mesh_terms: D045744:Cell Line, Tumor; D002945:Cisplatin / Q000494:pharmacology; D004260:DNA Repair; D015972:Gene Expression Regulation, Neoplastic; D024243:HMGB1 Protein / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D008175:Lung Neoplasms / Q000235:genetics / Q000378:metabolism*; D016159:Tumor Suppressor Protein p53 / Q000235:genetics / Q000378:metabolism*
chemical_list: D024243:HMGB1 Protein; C585491:HMGB1 protein, human; C495901:TP53 protein, human; D016159:Tumor Suppressor Protein p53; D002945:Cisplatin
keywords: DNA repair; HMGB1; cisplatin; lung cancer; p53