HMGA proteins promote ATM expression and enhance cancer cell resistance to genotoxic agents. (Articolo in rivista)

Type
Label
  • HMGA proteins promote ATM expression and enhance cancer cell resistance to genotoxic agents. (Articolo in rivista) (literal)
Anno
  • 2011-01-01T00:00:00+01:00 (literal)
Alternative label
  • Palmieri D, Valentino T, D'Angelo D, De Martino I, Postiglione I, Pacelli R, Croce CM, Fedele M, Fusco A. (2011)
    HMGA proteins promote ATM expression and enhance cancer cell resistance to genotoxic agents.
    in Oncogene (Basingstoke)
    (literal)
Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#autori
  • Palmieri D, Valentino T, D'Angelo D, De Martino I, Postiglione I, Pacelli R, Croce CM, Fedele M, Fusco A. (literal)
Pagina inizio
  • 3024 (literal)
Pagina fine
  • 3035 (literal)
Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#numeroVolume
  • 27 (literal)
Rivista
Note
  • ISI Web of Science (WOS) (literal)
Titolo
  • HMGA proteins promote ATM expression and enhance cancer cell resistance to genotoxic agents. (literal)
Abstract
  • DNA-damaging therapies represent a keystone in cancer treatment. Unfortunately, many tumors often relapse because of a group of cancer cells, which are resistant to conventional therapies. High-mobility group A (HMGA) proteins has a key role in cell transformation, and their overexpression is a common feature of human malignant neoplasias, representing a poor prognostic index often correlated to anti-cancer drug resistance. Our previous results demonstrated that HMGA1 is a substrate of ataxia-telangiectasia mutated (ATM), the main cellular sensor of genotoxic stress. Here we also report thatHMGA2, the other member of the HMGA family, is a novel substrate of ATM. Interestingly, we found that HMGA proteins positively regulate ATM gene expression. Moreover, induction of ATM kinase activity by DNA-damaging agents enhances HMGA-dependent transcriptional activation of ATM promoter, suggesting that ATM expression is modulated by a DNA-damage- and HMGA-dependent positive feedback loop. Finally, inhibition of HMGA expression in mouse embryonic fibroblasts and in cancer cells strongly reduces ATM protein levels, impairing the cellular DNA-damage response and enhancing the sensitivity to DNA-damaging agents. These findings indicate this novel HMGA-ATM pathway as a new potential target to improve the effectiveness of conventional anti-neoplastic treatments on the genotoxic-drug resistant cancer cells.Oncogene advance online publication, 21 February 2011; doi:10.1038/onc.2011.21. (literal)
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