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Emerging Role of Oxidative Stress on EGFR and OGG1-BER Cross-Regulation: Implications in Thyroid Physiopathology.
Moscatello, Carmelo; Di Marcantonio, Maria Carmela; Savino, Luca; D'Amico, Emira; Spacco, Giordano; Simeone, Pasquale; Lanuti, Paola; Muraro, Raffaella; Mincione, Gabriella; Cotellese, Roberto; Aceto, Gitana Maria.
Afiliación
  • Moscatello C; Department of Medical, Oral and Biotechnological Sciences, University "G. d'Annunzio" Chieti-Pescara, Via dei Vestini 31, 66100 Chieti, Italy.
  • Di Marcantonio MC; Department of Innovative Technologies in Medicine & Dentistry, University "G. d'Annunzio", Chieti-Pescara, Via dei Vestini 31, 66100 Chieti, Italy.
  • Savino L; Department of Innovative Technologies in Medicine & Dentistry, University "G. d'Annunzio", Chieti-Pescara, Via dei Vestini 31, 66100 Chieti, Italy.
  • D'Amico E; Department of Medical, Oral and Biotechnological Sciences, University "G. d'Annunzio" Chieti-Pescara, Via dei Vestini 31, 66100 Chieti, Italy.
  • Spacco G; Department of Medical, Oral and Biotechnological Sciences, University "G. d'Annunzio" Chieti-Pescara, Via dei Vestini 31, 66100 Chieti, Italy.
  • Simeone P; Department of Medicine and Aging Sciences, University "G. d'Annunzio", Chieti-Pescara, 66100 Chieti, Italy.
  • Lanuti P; Center for Advanced Studies and Technology (C.A.S.T.) at University "G. d'Annunzio", Chieti-Pescara, 66100 Chieti, Italy.
  • Muraro R; Department of Medicine and Aging Sciences, University "G. d'Annunzio", Chieti-Pescara, 66100 Chieti, Italy.
  • Mincione G; Center for Advanced Studies and Technology (C.A.S.T.) at University "G. d'Annunzio", Chieti-Pescara, 66100 Chieti, Italy.
  • Cotellese R; Department of Innovative Technologies in Medicine & Dentistry, University "G. d'Annunzio", Chieti-Pescara, Via dei Vestini 31, 66100 Chieti, Italy.
  • Aceto GM; Department of Innovative Technologies in Medicine & Dentistry, University "G. d'Annunzio", Chieti-Pescara, Via dei Vestini 31, 66100 Chieti, Italy.
Cells ; 11(5)2022 02 26.
Article en En | MEDLINE | ID: mdl-35269445
ABSTRACT
Thyroid diseases have a complex and multifactorial aetiology. Despite the numerous studies on the signals referable to the malignant transition, the molecular mechanisms concerning the role of oxidative stress remain elusive. Based on its strong oxidative power, H2O2 could be responsible for the high level of oxidative DNA damage observed in cancerous thyroid tissue and hyperactivation of mitogen-activated protein kinase (MAPK) and PI3K/Akt, which mediate ErbB signaling. Increased levels of 8-oxoG DNA adducts have been detected in the early stages of thyroid cancer. These DNA lesions are efficiently recognized and removed by the base excision repair (BER) pathway initiated by 8-oxoG glycosylase1 (OGG1). This study investigated the relationships between the EGFR and OGG1-BER pathways and their mutual regulation following oxidative stress stimulus by H2O2 in human thyrocytes. We clarified the modulation of ErbB receptors and their downstream pathways (PI3K/Akt and MAPK/ERK) under oxidative stress (from H2O2) at the level of gene and protein expression, according to the mechanism defined in a human non-pathological cell system, Nthy-ori 3-1. Later, on the basis of the results obtained by gene expression cluster analysis in normal cells, we assessed the dysregulation of the relationships in a model of papillary thyroid cancer with RET/PTC rearrangement (TPC-1). Our observations demonstrated that a H2O2 stress may induce a physiological cross-regulation between ErbB and OGG1-BER pathways in normal thyroid cells (while this is dysregulated in the TPC-1 cells). Gene expression data also delineated that MUTYH gene could play a physiological role in crosstalk between ErbB and BER pathways and this function is instead lost in cancer cells. Overall, our data on OGG1 protein expression suggest that it was physiologically regulated in response to oxidative modulation of ErbB, and that these might be dysregulated in the signaling pathway involving AKT in the progression of thyroid malignancies with RET/PTC rearrangements.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Neoplasias de la Tiroides / ADN Glicosilasas Tipo de estudio: Prognostic_studies Límite: Humans Idioma: En Revista: Cells Año: 2022 Tipo del documento: Article País de afiliación: Italia

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Neoplasias de la Tiroides / ADN Glicosilasas Tipo de estudio: Prognostic_studies Límite: Humans Idioma: En Revista: Cells Año: 2022 Tipo del documento: Article País de afiliación: Italia
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