ArticleCarcinogenesis2009
Induction of intestinalization in human esophageal keratinocytes is a multistep process.
Article in Carcinogenesis, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.
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Who cites it
24 citing papers in PubMed, 42 citations in OpenAlex.
- The Ephrin B2 Receptor Tyrosine Kinase Is a Regulator of Proto-oncogene MYC and Molecular Programs Central to Barrett's Neoplasia.Gastroenterology · 2022Article
- SPT6 loss permits the transdifferentiation of keratinocytes into an intestinal fate that resembles Barrett's metaplasia.iScience · 2021Article
- Inhibition of NHE-1 Increases Smoke-Induced Proliferative Activity of Barrett's Esophageal Cell Line.International journal of molecular sciences · 2021Article
- The cyclical hit model: how paligenosis might establish the mutational landscape in Barrett's esophagus and esophageal adenocarcinoma.Current opinion in gastroenterology · 2019Review
- Are Gastric and Esophageal Metaplasia Relatives? The Case for Barrett's Stemming from SPEM.Digestive diseases and sciences · 2018Review
- CDX2 upregulates SLC26A3 gene expression in intestinal epithelial cells.American journal of physiology. Gastrointestinal and liver physiology · 2017Article
- Modeling Esophagitis Using Human Three-Dimensional Organotypic Culture System.The American journal of pathology · 2017Article
- Autophagy levels are elevated in barrett's esophagus and promote cell survival from acid and oxidative stress.Molecular carcinogenesis · 2016Article
- Wnt/β-Catenin Signaling Activation beyond Robust Nuclear β-Catenin Accumulation in Nondysplastic Barrett's Esophagus: Regulation via Dickkopf-1.Neoplasia (New York, N.Y.) · 2015Article
- Mechanisms of Barrett's oesophagus: intestinal differentiation, stem cells, and tissue models.Best practice & research. Clinical gastroenterology · 2015Review
- Modeling human gastrointestinal inflammatory diseases using microphysiological culture systems.Experimental biology and medicine (Maywood, N.J.) · 2014Review
- Dickkopf-1, the Wnt antagonist, is induced by acidic pH and mediates epithelial cellular senescence in human reflux esophagitis.American journal of physiology. Gastrointestinal and liver physiology · 2014Article
- A surprise cell of origin for Barrett's esophagus.Cancer biology & therapy · 2012Article
- Math1/Atoh1 contributes to intestinalization of esophageal keratinocytes by inducing the expression of Muc2 and Keratin-20.Digestive diseases and sciences · 2012Article
- Study of FoxA pioneer factor at silent genes reveals Rfx-repressed enhancer at Cdx2 and a potential indicator of esophageal adenocarcinoma development.PLoS genetics · 2011Article
- Cox2 and β-catenin/T-cell factor signaling intestinalize human esophageal keratinocytes when cultured under organotypic conditions.Neoplasia (New York, N.Y.) · 2011Article
- Ectopic Cdx2 expression in murine esophagus models an intermediate stage in the emergence of Barrett's esophagus.PloS one · 2011Article
- Article
- Characterization of squamous esophageal cells resistant to bile acids at acidic pH: implication for Barrett's esophagus pathogenesis.American journal of physiology. Gastrointestinal and liver physiology · 2011Article
- Reflux, Barrett's, and adenocarcinoma of the esophagus: can we disrupt the pathway?Journal of gastrointestinal surgery : official journal of the Society for Surgery of the Alimentary Tract · 2010Article
Corrections and comments
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Authors and funding
7 authors at 2 institutions in 1 country.
Funding
Abstract
Barrett's esophagus (BE) is the replacement of normal squamous esophageal mucosa with an intestinalized columnar epithelium. The molecular mechanisms underlying its development are not understood. Cdx2 is an intestine-specific transcription factor that is ectopically expressed in BE, but its role in this process is unclear. Herein, we describe a novel cell culture model for BE. Retroviral-mediated Cdx2 expression in immortalized human esophageal keratinocytes [EPC-human telomerase reverse transcriptase (hTERT)] could transiently be established but not maintained and was associated with a reduction in cell proliferation. Coexpression of cyclin D1, but not a dominant-negative p53, rescued proliferation in the Cdx2-expressing cells. Cdx2 expression in the EPC-hTERT.D1 cells decreased cell proliferation but did not induce intestinalization. We investigated for other treatments to enhance intestinalization and found that acidic culture conditions uniformly killed EPC-hTERT.D1.Cdx2 cells. However, treatment with 5-aza-2-deoxycytidine (5-AzaC) to demethylate epigenetically silenced genes did appear to be tolerated. Multiple Cdx2 target genes, markers of intestinal differentiation and markers of BE, were induced by this 5-AzaC treatment. More interestingly, the expression level of several of these genes was enhanced only in the EPC-hTERT.D1-Cdx2 cells treated with 5-AzaC. Two of these, SLC26a3/DRA (downregulated in adenoma) and Na+/H+ exchanger 2 (NHE2), were not previously known to be elevated in BE; however, we confirmed their elevation in BE tissue samples. 5-AzaC treatment also induced cell senescence, even at low doses. We conclude that ectopic proliferation signals, alterations in epigenetic gene regulation and the inhibition of tumor suppressor mechanisms are required for Cdx2-mediated intestinalization of human esophageal keratinocytes in BE.
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Registered trials
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