GATA4 blocks squamous epithelial cell gene expression in human esophageal squamous cells

Abstract GATA4 promotes columnar epithelial cell fate during gastric development. When ectopically expressed in the developing mouse forestomach, the tissue emerges as columnar-like rather than stratified squamous with gene expression changes that parallel those observed in the pre-malignant squamou...

Descripción completa

Guardado en:

Detalles Bibliográficos
Autores principales:	Roman Stavniichuk, Ann DeLaForest, Cayla A. Thompson, James Miller, Rhonda F. Souza, Michele A. Battle
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/4b402ea396e1408f980bb3562bad575b
Etiquetas:	Agregar Etiqueta Sin Etiquetas, Sea el primero en etiquetar este registro!

id	oai:doaj.org-article:4b402ea396e1408f980bb3562bad575b
record_format	dspace
spelling	oai:doaj.org-article:4b402ea396e1408f980bb3562bad575b2021-12-02T14:06:31ZGATA4 blocks squamous epithelial cell gene expression in human esophageal squamous cells10.1038/s41598-021-82557-x2045-2322https://doaj.org/article/4b402ea396e1408f980bb3562bad575b2021-02-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-82557-xhttps://doaj.org/toc/2045-2322Abstract GATA4 promotes columnar epithelial cell fate during gastric development. When ectopically expressed in the developing mouse forestomach, the tissue emerges as columnar-like rather than stratified squamous with gene expression changes that parallel those observed in the pre-malignant squamous to columnar metaplasia known as Barrett’s esophagus (BE). GATA4 mRNA up-regulation and gene amplification occur in BE and its associated cancer, esophageal adenocarcinoma (EAC), and GATA4 gene amplification correlates with poor patient outcomes. Here, we explored the effect of ectopic expression of GATA4 in mature human esophageal squamous epithelial cells. We found that GATA4 expression in esophageal squamous epithelial cells compromised squamous cell marker gene expression and up-regulated expression of the canonical columnar cell cytokeratin KRT8. We observed GATA4 occupancy in the p63, KRT5, and KRT15 promoters, suggesting that GATA4 directly represses expression of squamous epithelial cell marker genes. Finally, we verified GATA4 protein expression in BE and EAC and found that exposure of esophageal squamous epithelial cells to acid and bile, known BE risk factors, induced GATA4 mRNA expression. We conclude that GATA4 suppresses expression of genes marking the stratified squamous epithelial cell lineage and that this repressive action by GATA4 may have implications in BE and EAC.Roman StavniichukAnn DeLaForestCayla A. ThompsonJames MillerRhonda F. SouzaMichele A. BattleNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-13 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Roman Stavniichuk Ann DeLaForest Cayla A. Thompson James Miller Rhonda F. Souza Michele A. Battle GATA4 blocks squamous epithelial cell gene expression in human esophageal squamous cells
description	Abstract GATA4 promotes columnar epithelial cell fate during gastric development. When ectopically expressed in the developing mouse forestomach, the tissue emerges as columnar-like rather than stratified squamous with gene expression changes that parallel those observed in the pre-malignant squamous to columnar metaplasia known as Barrett’s esophagus (BE). GATA4 mRNA up-regulation and gene amplification occur in BE and its associated cancer, esophageal adenocarcinoma (EAC), and GATA4 gene amplification correlates with poor patient outcomes. Here, we explored the effect of ectopic expression of GATA4 in mature human esophageal squamous epithelial cells. We found that GATA4 expression in esophageal squamous epithelial cells compromised squamous cell marker gene expression and up-regulated expression of the canonical columnar cell cytokeratin KRT8. We observed GATA4 occupancy in the p63, KRT5, and KRT15 promoters, suggesting that GATA4 directly represses expression of squamous epithelial cell marker genes. Finally, we verified GATA4 protein expression in BE and EAC and found that exposure of esophageal squamous epithelial cells to acid and bile, known BE risk factors, induced GATA4 mRNA expression. We conclude that GATA4 suppresses expression of genes marking the stratified squamous epithelial cell lineage and that this repressive action by GATA4 may have implications in BE and EAC.
format	article
author	Roman Stavniichuk Ann DeLaForest Cayla A. Thompson James Miller Rhonda F. Souza Michele A. Battle
author_facet	Roman Stavniichuk Ann DeLaForest Cayla A. Thompson James Miller Rhonda F. Souza Michele A. Battle
author_sort	Roman Stavniichuk
title	GATA4 blocks squamous epithelial cell gene expression in human esophageal squamous cells
title_short	GATA4 blocks squamous epithelial cell gene expression in human esophageal squamous cells
title_full	GATA4 blocks squamous epithelial cell gene expression in human esophageal squamous cells
title_fullStr	GATA4 blocks squamous epithelial cell gene expression in human esophageal squamous cells
title_full_unstemmed	GATA4 blocks squamous epithelial cell gene expression in human esophageal squamous cells
title_sort	gata4 blocks squamous epithelial cell gene expression in human esophageal squamous cells
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/4b402ea396e1408f980bb3562bad575b
work_keys_str_mv	AT romanstavniichuk gata4blockssquamousepithelialcellgeneexpressioninhumanesophagealsquamouscells AT anndelaforest gata4blockssquamousepithelialcellgeneexpressioninhumanesophagealsquamouscells AT caylaathompson gata4blockssquamousepithelialcellgeneexpressioninhumanesophagealsquamouscells AT jamesmiller gata4blockssquamousepithelialcellgeneexpressioninhumanesophagealsquamouscells AT rhondafsouza gata4blockssquamousepithelialcellgeneexpressioninhumanesophagealsquamouscells AT micheleabattle gata4blockssquamousepithelialcellgeneexpressioninhumanesophagealsquamouscells
_version_	1718391960736104448

GATA4 blocks squamous epithelial cell gene expression in human esophageal squamous cells

Ejemplares similares