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PAX9 regulates squamous cell differentiation and carcinogenesis in the oro-oesophageal epithelium.

Publication ,  Journal Article
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
Published in: J Pathol
February 2018

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-oesophageal epithelium. However, its functional roles in differentiation and carcinogenesis remain unclear. In this study, Pax9 deficiency in mouse oesophagus promoted cell proliferation, delayed cell differentiation, and altered the global gene expression profile. Ethanol exposure downregulated PAX9 expression in human oesophageal epithelial cells in vitro and mouse forestomach and tongue in vivo. We further showed that PAX9 was downregulated in human oro-oesophageal squamous cell carcinoma (OESCC), and its downregulation 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, oesophagus, and forestomach. In conclusion, PAX9 regulates squamous cell differentiation in the oro-oesophageal epithelium. Alcohol drinking and promoter hypermethylation are associated with PAX9 silencing in human OESCC. PAX9 downregulation may contribute to alcohol-associated oro-oesophageal squamous cell carcinogenesis. Copyright © 2017 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

Duke Scholars

Published In

J Pathol

DOI

EISSN

1096-9896

Publication Date

February 2018

Volume

244

Issue

2

Start / End Page

164 / 175

Location

England

Related Subject Headings

  • Transcriptome
  • Tongue Neoplasms
  • Squamous Cell Carcinoma of Head and Neck
  • Signal Transduction
  • Risk Factors
  • Promoter Regions, Genetic
  • Pathology
  • Paired Box Transcription Factors
  • PAX9 Transcription Factor
  • Mice, Knockout
 

Citation

APA
Chicago
ICMJE
MLA
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Xiong, Z., Ren, S., Chen, H., Liu, Y., Huang, C., Zhang, Y. L., … Chen, X. (2018). PAX9 regulates squamous cell differentiation and carcinogenesis in the oro-oesophageal epithelium. J Pathol, 244(2), 164–175. https://doi.org/10.1002/path.4998
Xiong, Zhaohui, Shuang Ren, Hao Chen, Yao Liu, Caizhi Huang, Yawan Lyvia Zhang, Joab Otieno Odera, et al. “PAX9 regulates squamous cell differentiation and carcinogenesis in the oro-oesophageal epithelium.J Pathol 244, no. 2 (February 2018): 164–75. https://doi.org/10.1002/path.4998.
Xiong Z, Ren S, Chen H, Liu Y, Huang C, Zhang YL, et al. PAX9 regulates squamous cell differentiation and carcinogenesis in the oro-oesophageal epithelium. J Pathol. 2018 Feb;244(2):164–75.
Xiong, Zhaohui, et al. “PAX9 regulates squamous cell differentiation and carcinogenesis in the oro-oesophageal epithelium.J Pathol, vol. 244, no. 2, Feb. 2018, pp. 164–75. Pubmed, doi:10.1002/path.4998.
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. PAX9 regulates squamous cell differentiation and carcinogenesis in the oro-oesophageal epithelium. J Pathol. 2018 Feb;244(2):164–175.
Journal cover image

Published In

J Pathol

DOI

EISSN

1096-9896

Publication Date

February 2018

Volume

244

Issue

2

Start / End Page

164 / 175

Location

England

Related Subject Headings

  • Transcriptome
  • Tongue Neoplasms
  • Squamous Cell Carcinoma of Head and Neck
  • Signal Transduction
  • Risk Factors
  • Promoter Regions, Genetic
  • Pathology
  • Paired Box Transcription Factors
  • PAX9 Transcription Factor
  • Mice, Knockout