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

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

doi:10.1155/2021/3060375

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

Int J Dent. 2021 Dec 27:2021:3060375. doi: 10.1155/2021/3060375. eCollection 2021.

Affiliations

¹ Laboratory of Pathological Anatomy and Immunohistochemistry, School of Dentistry, Federal University of Pará, Belém, PA, Brazil.
² Cell Culture Laboratory, School of Dentistry, Federal University of Pará, Belém, PA, Brazil.
³ Health Science Institute, Federal University of Pará, Faculty of Nursing, Belém, PA, Brazil.
⁴ Biological Engineer Laboratory, Park of Science and Technology, Belém, PA, Brazil.
⁵ Department of Oral Surgery and Pathology, School of Dentistry, Federal University of Minas Gerais, Belo Horizonte, MG, Brazil.
⁶ Department of Orthodontics, Federal University of Pará, Faculty of Dentistry, Belém, PA, Brazil.

Abstract

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.