title: Oxidative stress and the subcellular localization of the telomerase reverse transcriptase (TERT) in papillary thyroid cancer.
abstract: During hormonogenesis, thyrocytes are physiologically exposed to high levels of oxidative stress (OS) which could either be involved in the pathogenesis of thyroid cancer or exert a cytotoxic effect. We analyzed the oxidative status of papillary thyroid cancer (PTC) both directly, by measuring H2O2 generation by NADPH oxidases (NOXs), and indirectly, by evaluating the antioxidant activity of glutathione peroxidase (GPX), which neutralizes H2O2 excess, and the lipid peroxidation (LP). Moreover, we investigated the subcellular localization of telomerase reverse transcriptase (TERT), and the H2O2 levels in the mitochondria of tumor and normal tissues. The calcium-dependent and independent H2O2 generation activity was significantly higher in tumors than in normal tissues. The GPX activity was higher in PTCs than in normal tissues, and, consistently, no differences were found in LP levels. Moreover, while TERT nuclear expression was similar in tumor and normal tissues, the mitochondrial localization was significantly higher in tumors. At the mitochondrial level, no differences were found in H2O2 generation between tumor and normal tissues. In conclusion, present data demonstrate that the intracellular H2O2 generation by NOXs is significantly higher in PTCs than in normal thyroid tissues. The increased GPX activity found in tumors counteracts the potential cytotoxic effects of high OS exposure. The significantly higher mitochondrial localization of TERT in tumors is consistent with its shuttling from the nucleus upon exposure to high OS. Finally, mitochondrial OS was not significantly different in tumors and normal tissues, supporting the postulated role of mitochondrial TERT in the control of local H2O2 production.
authors.affiliation: Endocrine Unit, Fondazione IRCCS Ca' Granda, Milan, Italy; Department of Clinical Sciences and Community Health, University of Milan, Milan, Italy.
authors.forename: Marina
authors.initials: M
authors.lastname: Muzza
authors.affiliation: Endocrine Unit, Fondazione IRCCS Ca' Granda, Milan, Italy; Department of Clinical Sciences and Community Health, University of Milan, Milan, Italy.
authors.forename: Carla
authors.initials: C
authors.lastname: Colombo
authors.affiliation: Endocrine Unit, Fondazione IRCCS Ca' Granda, Milan, Italy; Department of Pathophysiology and Transplantation, University of Milan, Milan, Italy.
authors.forename: Valentina
authors.initials: V
authors.lastname: Cirello
authors.affiliation: Endocrine Unit, Fondazione IRCCS Ca' Granda, Milan, Italy; Department of Clinical Sciences and Community Health, University of Milan, Milan, Italy.
authors.forename: Michela
authors.initials: M
authors.lastname: Perrino
authors.affiliation: Endocrine Surgery Unit, Fondazione IRCCS Ca' Granda, Milan, Italy.
authors.forename: Leonardo
authors.initials: L
authors.lastname: Vicentini
authors.affiliation: Endocrine Unit, Fondazione IRCCS Ca' Granda, Milan, Italy; Department of Pathophysiology and Transplantation, University of Milan, Milan, Italy. Electronic address: laura.fugazzola@unimi.it.
authors.forename: Laura
authors.initials: L
authors.lastname: Fugazzola
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000975:Antioxidants / Q000378:metabolism; D002291:Carcinoma, Papillary / Q000378:metabolism* / Q000473:pathology*; D002467:Cell Nucleus / Q000378:metabolism; D005260:Female; D005979:Glutathione Peroxidase / Q000378:metabolism; D006801:Humans; D006861:Hydrogen Peroxide / Q000378:metabolism; D015227:Lipid Peroxidation / Q000502:physiology; D008297:Male; D008875:Middle Aged; D008928:Mitochondria / Q000378:metabolism; D019255:NADPH Oxidases / Q000378:metabolism; D010084:Oxidation-Reduction; D018384:Oxidative Stress / Q000502:physiology*; D019098:Telomerase / Q000378:metabolism*; D000077273:Thyroid Cancer, Papillary; D013964:Thyroid Neoplasms / Q000378:metabolism* / Q000473:pathology*
chemical_list: D000975:Antioxidants; D006861:Hydrogen Peroxide; D005979:Glutathione Peroxidase; D019255:NADPH Oxidases; C509186:TERT protein, human; D019098:Telomerase
keywords: DUOX; NOX; Oxidative stress; TERT; Thyroid cancer