Hypoxia-induced HIF-1α and ZEB1 are critical for the malignant transformation of ameloblastoma via TGF-ß-dependent EMT.
Cancer Med
; 8(18): 7822-7832, 2019 12.
Article
en En
| MEDLINE
| ID: mdl-31674718
ABSTRACT
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-ß (TGF-ß) 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-ß-dependent EMT. Then, both HIF-1α and ZEB1 could be potential biomarkers to predict the malignant transformation of AB.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Ameloblastoma
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Transformación Celular Neoplásica
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Factor de Crecimiento Transformador beta
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Subunidad alfa del Factor 1 Inducible por Hipoxia
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Transición Epitelial-Mesenquimal
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Homeobox 1 de Unión a la E-Box con Dedos de Zinc
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Hipoxia
Tipo de estudio:
Prognostic_studies
Límite:
Adolescent
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Adult
/
Aged
/
Female
/
Humans
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Male
/
Middle aged
Idioma:
En
Revista:
Cancer Med
Año:
2019
Tipo del documento:
Article
País de afiliación:
Japón