IKKβ overexpression together with a lack of tumour suppressor genes causes ameloblastic odontomas in mice.
10.1038/s41368-019-0067-9
- Author:
Angustias PAGE
1
;
Ana BRAVO
2
;
Cristian SUAREZ-CABRERA
1
;
Raquel SANCHEZ-BALTASAR
1
;
Marta OTEO
3
;
Miguel Angel MORCILLO
3
;
M Llanos CASANOVA
1
;
Jose C SEGOVIA
4
;
Manuel NAVARRO
1
;
Angel RAMIREZ
5
Author Information
1. Molecular Oncology Unit. Centro de Investigaciones Energéticas, Medioambientales y Tecnológicas (CIEMAT), Madrid, Spain.
2. Department of Anatomy, Animal Production and Veterinary Clinical Sciences, Laboratory of Pathology Phenotyping of Genetically Engineered Mice, Faculty of Veterinary Medicine, University of Santiago de Compostela, Lugo, Spain.
3. Biomedical Applications and Pharmacokinetics Unit, Centro de Investigaciones Energéticas, Medioambientales y Tecnológicas (CIEMAT), Madrid, Spain.
4. Hematopoietic Innovative Therapies Division. Centro de Investigaciones Energéticas, Medioambientales y Tecnológicas (CIEMAT). Centro de Investigación Biomédica en Red de Enfermedades Raras (CIBERER), Madrid, Spain.
5. Molecular Oncology Unit. Centro de Investigaciones Energéticas, Medioambientales y Tecnológicas (CIEMAT), Madrid, Spain. a.ramirez@ciemat.es.
- Publication Type:Journal Article
- From:
International Journal of Oral Science
2020;12(1):1-1
- CountryChina
- Language:English
-
Abstract:
Odontogenic tumours are a heterogeneous group of lesions that develop in the oral cavity region and are characterized by the formation of tumoural structures that differentiate as teeth. Due to the diversity of their histopathological characteristics and clinical behaviour, the classification of these tumours is still under debate. Alterations in morphogenesis pathways such as the Hedgehog, MAPK and WNT/β-catenin pathways are implicated in the formation of odontogenic lesions, but the molecular bases of many of these lesions are still unknown. In this study, we used genetically modified mice to study the role of IKKβ (a fundamental regulator of NF-κB activity and many other proteins) in oral epithelial cells and odontogenic tissues. Transgenic mice overexpressing IKKβ in oral epithelial cells show a significant increase in immune cells in both the oral epithelia and oral submucosa. They also show changes in the expression of several proteins and miRNAs that are important for cancer development. Interestingly, we found that overactivity of IKKβ in oral epithelia and odontogenic tissues, in conjunction with the loss of tumour suppressor proteins (p53, or p16 and p19), leads to the appearance of odontogenic tumours that can be classified as ameloblastic odontomas, sometimes accompanied by foci of secondary ameloblastic carcinomas. These tumours show NF-κB activation and increased β-catenin activity. These findings may help to elucidate the molecular determinants of odontogenic tumourigenesis and the role of IKKβ in the homoeostasis and tumoural transformation of oral and odontogenic epithelia.
