Hnf4α is a key gene that can generate columnar metaplasia in oesophageal epithelium
| Autor: | Jonathan M. Quinlan, Zoë D. Burke, Yu Chen, Ramiro Jover, Leonard P. Griffiths, David Tosh, Stephen G. Ward, J. Mark Farrant, M Bock, Jonathan M.W. Slack, Leigh Biddlestone, Wei-Yuan Yu, Benjamin J. Colleypriest |
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| Jazyk: | angličtina |
| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
Male Pathology Cancer Research Esophageal Neoplasms Biopsy Epithelium Mice 0302 clinical medicine Metaplasia CDX2 Transcription Factor CDX2 Càncer Oesophageal cancer Anatomy Neoplasm Proteins Barrett's oesophagus Gene Expression Regulation Neoplastic medicine.anatomical_structure Hepatocyte Nuclear Factor 4 Loricrin 030211 gastroenterology & hepatology medicine.symptom Villin Hepatocyte nuclear factor 4-alpha Adult medicine.medical_specialty Stratified squamous epithelium Biology Adenocarcinoma Organ culture Article 03 medical and health sciences Barrett Esophagus Esophagus Organ Culture Techniques SDG 3 - Good Health and Well-being medicine Animals Humans Molecular Biology HNF4α Histologia Cell Biology digestive system diseases 030104 developmental biology biology.protein Ectopic expression Developmental Biology |
| Zdroj: | Colleypriest, Benjamin J. Burke, Zoë D. Griffiths, Leonard P. Chen, Yu Yu, Wei-Yuan Jover Atienza, Ramiro Bock, Michael Biddlestone, Leigh Quinlan, Jonathan M. Ward, Stephen G. Mark Farrant, J. Slack, Jonathan M.W. Tosh, David 2017 Hnf4α is a key gene that can generate columnar metaplasia in oesophageal epithelium Differentiation 93 39 49 Differentiation; Research in Biological Diversity Colleypriest, B J, Burke, Z D, Griffiths, L P, Chen, Y, Yu, W-Y, Jover, R, Bock, M, Biddlestone, L, Quinlan, J M, Ward, S G, Mark Farrant, J, Slack, J M W & Tosh, D 2017, ' Hnf4α is a key gene that can generate columnar metaplasia in oesophageal epithelium ', Differentiation, vol. 93, pp. 39-49 . https://doi.org/10.1016/j.diff.2016.11.001 RODERIC. Repositorio Institucional de la Universitat de Valéncia instname |
| DOI: | 10.1016/j.diff.2016.11.001 |
| Popis: | Barrett's metaplasia is the only known morphological precursor to oesophageal adenocarcinoma and is characterized by replacement of stratified squamous epithelium by columnar epithelium. The cell of origin is uncertain and the molecular mechanisms responsible for the change in cellular phenotype are poorly understood. We therefore explored the role of two transcription factors, Cdx2 and HNF4α in the conversion using primary organ cultures. Biopsy samples from cases of human Barrett's metaplasia were analysed for the presence of CDX2 and HNF4α. A new organ culture system for adult murine oesophagus is described. Using this, Cdx2 and HNF4α were ectopically expressed by adenoviral infection. The phenotype following infection was determined by a combination of PCR, immunohistochemical and morphological analyses. We demonstrate the expression of CDX2 and HNF4α in human biopsy samples. Our oesophageal organ culture system expressed markers characteristic of the normal SSQE: p63, K14, K4 and loricrin. Ectopic expression of HNF4α, but not of Cdx2 induced expression of Tff3, villin, K8 and E-cadherin. HNF4α is sufficient to induce a columnar-like phenotype in adult mouse oesophageal epithelium and is present in the human condition. These data suggest that induction of HNF4α is a key early step in the formation of Barrett's metaplasia and are consistent with an origin of Barrett's metaplasia from the oesophageal epithelium. |
| Databáze: | OpenAIRE |
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