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Lookup NU author(s): Dr Ralf KistORCiD, Dr Heiko Peters
This is the authors' accepted manuscript of an article that has been published in its final definitive form by John Wiley & Sons Ltd, 2018.
For re-use rights please refer to the publisher's terms and conditions.
PAX9 is a transcription factor of the PAX family characterized by a DNA-binding paired domain. Previous studies have suggested a potential role of PAX9 in squamous cell differentiation and carcinogenesis of the oro-esophageal epithelium. However, its functional roles in differentiation and carcinogenesis remain unclear. In this study, Pax9 deficiency in the mouse esophagus promoted cell proliferation, delayed cell differentiation and altered the global gene expression profile. Ethanol exposure down-regulated PAX9 expression in human esophageal epithelial cells in vitro and mouse forestomach and tongue in vivo. We further showed that PAX9 was down-regulated in human oro-esophageal squamous cell carcinoma (OESCC), and its down-regulation was associated with alcohol drinking and promoter hypermethylation. Moreover, ad libitum feeding with a liquid diet containing ethanol for 40 weeks or Pax9 deficiency promoted N-nitrosomethylbenzylamine-induced squamous cell carcinogenesis in mouse tongue, esophagus, and forestomach. In conclusion, PAX9 regulates squamous cell differentiation in the oro-esophageal epithelium. Alcohol drinking and promoter hypermethylation are associated with PAX9 silencing in human OESCC. PAX9 down-regulation may contribute to alcohol-associated oro-esophageal squamous cell carcinogenesis.
Author(s): Xiong Z, Ren S, Chen H, Liu Y, Huang C, Zhang YL, Odera JO, Chen T, Kist R, Peters H, Garman K, Sun Z, Chen X
Publication type: Article
Publication status: Published
Journal: Journal of Pathology
Year: 2018
Volume: 244
Issue: 2
Pages: 164-175
Print publication date: 01/02/2018
Online publication date: 21/10/2017
Acceptance date: 21/10/2017
Date deposited: 09/11/2017
ISSN (print): 0022-3417
ISSN (electronic): 1096-9896
Publisher: John Wiley & Sons Ltd
URL: https://doi.org/10.1002/path.4998
DOI: 10.1002/path.4998
PubMed id: 29055049
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