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Hnf4α is a key gene that can generate columnar metaplasia in oesophageal epithelium

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Hnf4α is a key gene that can generate columnar metaplasia in oesophageal epithelium

dc.contributor.author	Colleypriest, Benjamin J.
dc.contributor.author	Burke, Zoë D.
dc.contributor.author	Griffiths, Leonard P.
dc.contributor.author	Chen, Yu
dc.contributor.author	Yu, Wei-Yuan
dc.contributor.author	Jover Atienza, Ramiro
dc.contributor.author	Bock, Michael
dc.contributor.author	Biddlestone, Leigh
dc.contributor.author	Quinlan, Jonathan M.
dc.contributor.author	Ward, Stephen G.
dc.contributor.author	Mark Farrant, J.
dc.contributor.author	Slack, Jonathan M.W.
dc.contributor.author	Tosh, David
dc.date.accessioned	2018-04-19T15:15:33Z
dc.date.available	2018-04-19T15:15:33Z
dc.date.issued	2017
dc.identifier.uri	http://hdl.handle.net/10550/65810
dc.description.abstract	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.
dc.language.iso	eng
dc.relation.ispartof	Differentiation, 2017, vol. 93, p. 39-49
dc.rights.uri	info:eu-repo/semantics/openAccess
dc.source	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
dc.subject	Càncer
dc.subject	Histologia
dc.title	Hnf4α is a key gene that can generate columnar metaplasia in oesophageal epithelium
dc.type	info:eu-repo/semantics/article
dc.date.updated	2018-04-19T15:15:34Z
dc.identifier.doi	https://doi.org/10.1016/j.diff.2016.11.001
dc.identifier.idgrec	125157