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dc.contributor.author
Di Maso, Vittorio
dc.contributor.author
Mediavilla, Maria Gabriela
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dc.contributor.author
Vascotto, Carlo
dc.contributor.author
Lupo, Francesco
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Baccarani, Umberto
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Avellini, Claudio
dc.contributor.author
Tell, Gianluca
dc.contributor.author
Tiribelli, Claudio
dc.contributor.author
Crocè, Lory Saveria
dc.date.available
2020-01-09T21:22:36Z
dc.date.issued
2015-12
dc.identifier.citation
Di Maso, Vittorio; Mediavilla, Maria Gabriela; Vascotto, Carlo; Lupo, Francesco; Baccarani, Umberto; et al.; Transcriptional Up-Regulation of APE1/Ref-1 in hepatic tumor: Role in hepatocytes resistance to oxidative stress and apoptosis; Public Library of Science; Plos One; 10; 12; 12-2015; 1-14
dc.identifier.issn
1932-6203
dc.identifier.uri
http://hdl.handle.net/11336/94265
dc.description.abstract
Objective Human Hepatocellular Carcinoma (HCC) is the fifth most frequent neoplasm worldwide and the most serious complication of long-standing chronic liver diseases (CLD). Its development is associated with chronic inflammation and sustained oxidative stress. Deregulation of apurinic apyrimidinic endonuclease 1/redox effector factor 1 (APE1/Ref-1), a master regulator of cellular response to oxidative stress, has been associated with poor prognosis in several cancers including HCC. Design In the present study we investigated the APE1/Ref-1 mRNA levels in cirrhotic and HCC tissues obtained during HCC resection. The possible protective role of APE1/Ref-1 against oxidative stress and apoptosis was evaluated in vitro in immortalized human hepatocytes (IHH) over-expressing APE1/Ref-1. Results APE1/Ref-1 was up-regulated in HCC, regulation occurring at the transcriptional level. APE1/Ref-1 mRNA content increased with the progression of liver disease with the transcriptional up-regulation present in cirrhosis significantly increased in HCC. The up-regulation was higher in the less differentiated cancers. In vitro, over-expression of APE1/Ref-1 in normal hepatocytes conferred cell protection against oxidative stress and it was associated with BAX inhibition and escape from apoptosis. Conclusion APE1/Ref-1 is up-regulated in HCC and this over-expression correlates with cancer aggressiveness. The up-regulation occurs at the transcriptional level and it is present in the earliest phases of hepatocarcinogenesis. The APE-1/Ref-1 over-expression is associated with hepatocyte survival and inhibits BAX activation and apoptosis. These data suggest a possible role of APE1/Ref-1 over-expression both in hepatocyte survival and HCC development calling attention to this molecule as a promising marker for HCC diagnosis and treatment.
dc.format
application/pdf
dc.language.iso
eng
dc.publisher
Public Library of Science
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dc.rights
info:eu-repo/semantics/openAccess
dc.rights.uri
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
dc.subject
HEPATOCELLULAR CARCINOMA
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OXIDATIVE STRESS
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APOPTOSIS
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CHRONIC LIVER DISEASE
dc.subject.classification
Oncología
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dc.subject.classification
Medicina Clínica
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dc.subject.classification
CIENCIAS MÉDICAS Y DE LA SALUD
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dc.title
Transcriptional Up-Regulation of APE1/Ref-1 in hepatic tumor: Role in hepatocytes resistance to oxidative stress and apoptosis
dc.type
info:eu-repo/semantics/article
dc.type
info:ar-repo/semantics/artículo
dc.type
info:eu-repo/semantics/publishedVersion
dc.date.updated
2020-01-09T17:35:05Z
dc.journal.volume
10
dc.journal.number
12
dc.journal.pagination
1-14
dc.journal.pais
Estados Unidos
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dc.journal.ciudad
San Francisco
dc.description.fil
Fil: Di Maso, Vittorio. Fondazione Italiana Fegato Area Science Park Basovizza; Italia
dc.description.fil
Fil: Mediavilla, Maria Gabriela. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Rosario. Instituto de Biología Molecular y Celular de Rosario. Universidad Nacional de Rosario. Facultad de Ciencias Bioquímicas y Farmacéuticas. Instituto de Biología Molecular y Celular de Rosario; Argentina
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Fil: Vascotto, Carlo. Universidad de Udine; Italia
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Fil: Lupo, Francesco. Universidad de Torino; Italia
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Fil: Baccarani, Umberto. Universidad de Udine; Italia
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Fil: Avellini, Claudio. Universidad de Udine; Italia
dc.description.fil
Fil: Tell, Gianluca. Fondazione Italiana Fegato Area Science Park Basovizza; Italia
dc.description.fil
Fil: Tiribelli, Claudio. Università degli Studi di Trieste; Italia. Fondazione Italiana Fegato Area Science Park Basovizza; Italia
dc.description.fil
Fil: Crocè, Lory Saveria. Università degli Studi di Trieste; Italia. Fondazione Italiana Fegato Area Science Park Basovizza; Italia
dc.journal.title
Plos One
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dc.relation.alternativeid
info:eu-repo/semantics/altIdentifier/url/https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0143289
dc.relation.alternativeid
info:eu-repo/semantics/altIdentifier/doi/http://dx.doi.org/10.1371/journal.pone.0143289
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