Ameloblastic carcinoma (AC) is defined as a rare primary epithelial odontogenic 
malignant neoplasm and the malignant counterpart of benign epithelial 
odontogenic tumor of ameloblastoma (AB) by the WHO classification. AC develops 
pulmonary metastasis in about one third of the patients and reveals a poor 
prognosis. However, the mechanisms of AC oncogenesis remain unclear. In this 
report, we aimed to clarify the mechanisms of malignant transformation of AB or 
AC carcinogenesis. The relatively important genes in the malignant 
transformation of AB were screened by DNA microarray analysis, and the 
expression and localization of related proteins were examined by 
immunohistochemistry using samples of AB and secondary AC. Two genes of 
hypoxia-inducible factor 1 alpha subunit (HIF1A) and zinc finger E-box-binding 
homeobox 1 (ZEB1) were significantly and relatively upregulated in AC than in 
AB. Both genes were closely related in hypoxia and epithelial-mesenchymal 
transition (EMT). In addition, expressions of HIF-1α and ZEB1 proteins were 
significantly stronger in AC than in AB. In the cell assays using ameloblastoma 
cell line, AM-1, hypoxia condition upregulated the expression of transforming 
growth factor-β (TGF-β) and induced EMT. Furthermore, the hypoxia-induced 
morphological change and cell migration ability were inhibited by an 
antiallergic medicine tranilast. Finally, we concluded that hypoxia-induced 
HIF-1α and ZEB1 were critical for the malignant transformation of AB via 
TGF-β-dependent EMT. Then, both HIF-1α and ZEB1 could be potential biomarkers to 
predict the malignant transformation of AB.