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Cdx1 and c-Myc Foster the Initiation of Transdifferentiation of the Normal Esophageal Squamous Epithelium toward Barrett's Esophagus
- Source :
- PLoS ONE, Vol 3, Iss 10, p e3534 (2008), PLoS ONE
- Publication Year :
- 2008
- Publisher :
- Public Library of Science (PLoS), 2008.
-
Abstract
- Background: Barrett’s esophagus is a premalignant condition whereby the normal stratified squamous esophageal epithelium undergoes a transdifferentiation program resulting in a simple columnar epithelium reminiscent of the small intestine. These changes are typically associated with the stratified squamous epithelium chronically exposed to acid and bile salts as a result of gastroesophageal reflux disease (GERD). Despite this well-defined epidemiologic association between acid reflux and Barrett’s esophagus, the genetic changes that induce this transdifferentiation process in esophageal keratinocytes have remained undefined. Methodology/Principal Findings: To begin to identify the genetic changes responsible for transdifferentiaiton in Barrett’s esophagus, we performed a microarray analysis of normal esophageal, Barrett’s esophagus and small intestinal biopsy specimens to identify candidate signaling pathways and transcription factors that may be involved. Through this screen we identified the Cdx1 homeodomain transcription factor and the c-myc pathway as possible candidates. Cdx1 and c-myc were then tested for their ability to induce transdifferentiation in immortalized human esophageal keratinocytes using organotypic culturing methods. Analyses of these cultures reveal that c-myc and cdx1 cooperate to induce mucin production and changes in keratin expression that are observed in the epithelium of Barrett’s esophagus. Conclusions/Significance: These data demonstrate the ability of Cdx1 and c-myc to initiate the earliest stages of transdifferentiation of esophageal keratinocytes toward a cell fate characteristic of Barrett’s esophagus.
- Subjects :
- Keratinocytes
Pathology
medicine.medical_specialty
Gastroenterology and Hepatology/Gastrointestinal Cancers
Esophageal Neoplasms
lcsh:Medicine
Stratified squamous epithelium
Biology
Proto-Oncogene Proteins c-myc
Barrett Esophagus
Esophagus
Simple columnar epithelium
medicine
Cluster Analysis
Humans
lcsh:Science
Cells, Cultured
Oligonucleotide Array Sequence Analysis
Homeodomain Proteins
Multidisciplinary
Gene Expression Profiling
lcsh:R
Transdifferentiation
medicine.disease
digestive system diseases
Epithelium
medicine.anatomical_structure
Cell Transdifferentiation
Barrett's esophagus
Developmental Biology/Cell Differentiation
Carcinoma, Squamous Cell
GERD
lcsh:Q
Gastroenterology and Hepatology/Esophagus
Precancerous Conditions
Biomarkers
Research Article
Subjects
Details
- ISSN :
- 19326203
- Volume :
- 3
- Database :
- OpenAIRE
- Journal :
- PLoS ONE
- Accession number :
- edsair.doi.dedup.....77eef98ecaf7e804c2798f389bd42ca0
- Full Text :
- https://doi.org/10.1371/journal.pone.0003534