HIF-1α Is Associated with Resistance to Hypoxia-Induced Apoptosis in Ameloblastoma

Background. Ameloblastoma (AMB) is a benign odontogenic tumour, with an aggressive local behaviour and a high rate of recurrence. Previous studies have demonstrated that hypoxia-induced factor alpha 1 (HIF-1α) and activated caspase-3 contribute to tumour invasiveness and cytogenesis in ameloblastoma...

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Main Authors: Katherine Julissa Palma Valladares, Karolyny Martins Balbinot, Antonia Taiane Lopes de Moraes, Maria Sueli da Silva Kataoka, Aline Maria Pereira Cruz Ramos, Rommel Thiago Jucá Ramos, Artur Luiz da Costa da Silva, Ricardo Alves Mesquita, David Normando, Sérgio de Melo Alves Júnior, João de Jesus Viana Pinheiro
Format: Article
Language:English
Published: Wiley 2021-01-01
Series:International Journal of Dentistry
Online Access:http://dx.doi.org/10.1155/2021/3060375
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author Katherine Julissa Palma Valladares
Karolyny Martins Balbinot
Antonia Taiane Lopes de Moraes
Maria Sueli da Silva Kataoka
Aline Maria Pereira Cruz Ramos
Rommel Thiago Jucá Ramos
Artur Luiz da Costa da Silva
Ricardo Alves Mesquita
David Normando
Sérgio de Melo Alves Júnior
João de Jesus Viana Pinheiro
author_facet Katherine Julissa Palma Valladares
Karolyny Martins Balbinot
Antonia Taiane Lopes de Moraes
Maria Sueli da Silva Kataoka
Aline Maria Pereira Cruz Ramos
Rommel Thiago Jucá Ramos
Artur Luiz da Costa da Silva
Ricardo Alves Mesquita
David Normando
Sérgio de Melo Alves Júnior
João de Jesus Viana Pinheiro
author_sort Katherine Julissa Palma Valladares
collection DOAJ
description Background. Ameloblastoma (AMB) is a benign odontogenic tumour, with an aggressive local behaviour and a high rate of recurrence. Previous studies have demonstrated that hypoxia-induced factor alpha 1 (HIF-1α) and activated caspase-3 contribute to tumour invasiveness and cytogenesis in ameloblastoma. Hypoxia increases HIF-1α levels, which triggers a number of signalling pathways. This paper aimed to present data in the study of hypoxia-activated signalling pathways that modulate proapoptotic and antiapoptotic events in AMB. Methods. Twenty cases of AMB and ten cases of dental follicle (DF) were used to analyse the immunoexpression of HIF-1α, p53, BNIP3, Bcl-2, IAP-2, GLUT1, and Bax. To contribute to the study, an analysis of expression and genetic interaction was performed using the cell line AME-1. Results. AMB and DF expressed the studied proteins. These proteins showed significantly greater immunoexpression in AMB compared with the DF (p<0.05). HIF-1α showed an important association with GLUT1, and a positive correlation was observed among p53, Bcl-2, and IAP-2. Transcriptomic analysis showed the significant expression of the studied proteins, and the network generated showed a direct association of HIF-1αF with GLUT1 (SLC2A1), TP53, and LDHA. Interestingly, GLUT1 also exhibited direct interaction with TP53 and LDHA. Conclusion. In AMB tumorigenesis, hypoxia is possibly related to antiapoptotic events, which suggests an important role for HIF-1α, GLUT1, Bcl-2, IAP-2, and possibly p53.
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spelling doaj-art-5ce17aa006304f38ba88211be8fc8ea22025-02-03T01:04:11ZengWileyInternational Journal of Dentistry1687-87362021-01-01202110.1155/2021/3060375HIF-1α Is Associated with Resistance to Hypoxia-Induced Apoptosis in AmeloblastomaKatherine Julissa Palma Valladares0Karolyny Martins Balbinot1Antonia Taiane Lopes de Moraes2Maria Sueli da Silva Kataoka3Aline Maria Pereira Cruz Ramos4Rommel Thiago Jucá Ramos5Artur Luiz da Costa da Silva6Ricardo Alves Mesquita7David Normando8Sérgio de Melo Alves Júnior9João de Jesus Viana Pinheiro10Laboratory of Pathological Anatomy and ImmunohistochemistryLaboratory of Pathological Anatomy and ImmunohistochemistryCell Culture LaboratoryCell Culture LaboratoryHealth Science InstituteBiological Engineer LaboratoryBiological Engineer LaboratoryDepartment of Oral Surgery and PathologyDepartment of OrthodonticsLaboratory of Pathological Anatomy and ImmunohistochemistryCell Culture LaboratoryBackground. Ameloblastoma (AMB) is a benign odontogenic tumour, with an aggressive local behaviour and a high rate of recurrence. Previous studies have demonstrated that hypoxia-induced factor alpha 1 (HIF-1α) and activated caspase-3 contribute to tumour invasiveness and cytogenesis in ameloblastoma. Hypoxia increases HIF-1α levels, which triggers a number of signalling pathways. This paper aimed to present data in the study of hypoxia-activated signalling pathways that modulate proapoptotic and antiapoptotic events in AMB. Methods. Twenty cases of AMB and ten cases of dental follicle (DF) were used to analyse the immunoexpression of HIF-1α, p53, BNIP3, Bcl-2, IAP-2, GLUT1, and Bax. To contribute to the study, an analysis of expression and genetic interaction was performed using the cell line AME-1. Results. AMB and DF expressed the studied proteins. These proteins showed significantly greater immunoexpression in AMB compared with the DF (p<0.05). HIF-1α showed an important association with GLUT1, and a positive correlation was observed among p53, Bcl-2, and IAP-2. Transcriptomic analysis showed the significant expression of the studied proteins, and the network generated showed a direct association of HIF-1αF with GLUT1 (SLC2A1), TP53, and LDHA. Interestingly, GLUT1 also exhibited direct interaction with TP53 and LDHA. Conclusion. In AMB tumorigenesis, hypoxia is possibly related to antiapoptotic events, which suggests an important role for HIF-1α, GLUT1, Bcl-2, IAP-2, and possibly p53.http://dx.doi.org/10.1155/2021/3060375
spellingShingle Katherine Julissa Palma Valladares
Karolyny Martins Balbinot
Antonia Taiane Lopes de Moraes
Maria Sueli da Silva Kataoka
Aline Maria Pereira Cruz Ramos
Rommel Thiago Jucá Ramos
Artur Luiz da Costa da Silva
Ricardo Alves Mesquita
David Normando
Sérgio de Melo Alves Júnior
João de Jesus Viana Pinheiro
HIF-1α Is Associated with Resistance to Hypoxia-Induced Apoptosis in Ameloblastoma
International Journal of Dentistry
title HIF-1α Is Associated with Resistance to Hypoxia-Induced Apoptosis in Ameloblastoma
title_full HIF-1α Is Associated with Resistance to Hypoxia-Induced Apoptosis in Ameloblastoma
title_fullStr HIF-1α Is Associated with Resistance to Hypoxia-Induced Apoptosis in Ameloblastoma
title_full_unstemmed HIF-1α Is Associated with Resistance to Hypoxia-Induced Apoptosis in Ameloblastoma
title_short HIF-1α Is Associated with Resistance to Hypoxia-Induced Apoptosis in Ameloblastoma
title_sort hif 1α is associated with resistance to hypoxia induced apoptosis in ameloblastoma
url http://dx.doi.org/10.1155/2021/3060375
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