Hnf4 alpha is a key gene that can generate columnar metaplasia in oesophageal epithelium

Autor: Colleypriest, Benjamin J., Burke, Zoe D., Griffiths, Leonard P., Chen, Yu, Yu, Wei-Yuan, Jover, Ramiro, Bock, Michael, Biddlestone, Leigh, Quinlan, Jonathan M., Ward, Stephen G., Farrant, J. Mark, Slack, Jonathan M. W., Tosh, David
Rok vydání: 2017
Předmět:
Zdroj: Differentiation
r-IIS La Fe. Repositorio Institucional de Producción Científica del Instituto de Investigación Sanitaria La Fe
instname
ISSN: 0301-4681
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 HNF4 alpha in the conversion using primary organ cultures. Biopsy samples from cases of human Barrett's metaplasia were analysed for the presence of CDX2 and HNF4 alpha. A new organ culture system for adult murine oesophagus is described. Using this, Cdx2 and HNF4 alpha 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 HNF4 alpha in human biopsy samples. Our oesophageal organ culture system expressed markers characteristic of the normal SSQE: p63, K14, K4 and loricrin. Ectopic expression of HNF4 alpha, but not of Cdx2 induced expression of Tff3, villin, K8 and E-cadherin. HNF4 alpha 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 HNF4 alpha 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
Externí odkaz: