HIF-1 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-1) and activated caspase-3 contribute to tumour invasiveness and cytogenesis in ameloblastoma. Hypoxia increases HIF-1 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-1, 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 ( < 0.05). HIF-1 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-1F 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-1, GLUT1, Bcl-2, IAP-2, and possibly p53.