Barrett's oesophagus is the replacement of normal squamous oesophageal epithelium with an intestinalized columnar epithelium. Although some insight has been gained as to what Barrett's oesophagus is, how this columnar epithelium emerges from within a stratified squamous epithelium remains an unanswered question. We have sought to determine whether oesophageal keratinocytes can be trans-differentiated into Barrett's oesophagus cells. Using an Affymetrix microarray, we found unexpectedly that gene-expression patterns in the Barrett's oesophagus were only slightly more similar to the normal small intestine than they were to the normal oesophagus. Thus gene-expression patterns suggest significant molecular similarities remain between Barrett's oesophagus cells and normal squamous oesophageal epithelium, despite their histological resemblance with intestine. We next determined whether directed expression of intestine-specific transcription factors could induce intestinalization of keratinocytes. Retroviral-mediated Cdx2 (Caudal-type homeobox 2) expression in immortalized human oesophageal keratinocytes engineered with human telomerase reverse transcriptase (EPC2-hTERT cells) could be established transiently, but not maintained, and was associated with a reduction in cell proliferation. Co-expression of cyclin D1 rescued proliferation in the Cdx2-expressing cells, but co-expression of dominant-negative p53 did not. Cdx2 expression in the EPC2-hTERT.D1 cells did not induce intestinalization. However, when combined with treatments that induce chromatin remodelling, there was a significant induction of Barrett's oesophagus-associated genes. Studies are ongoing to determine whether other intestinal transcription factors, either alone or in combination, can provoke greater intestinalization of oesophageal keratinocytes. We conclude that, on the basis of gene-expression patterns, Barrett's oesophagus epithelial cells may represent an intermediate between oesophageal keratinocytes and intestinal epithelial cells. Moreover, our findings suggest that it may be possible to induce Barrett's oesophagus epithelial cells from oesophageal keratinocytes by altering the expression of certain critical genes.
Skip Nav Destination
Article navigation
April 2010
- Cover Image
- PDF Icon PDF LinkFront Matter
- PDF Icon PDF LinkTable of Contents
Conference Article|
March 22 2010
Modelling Barrett's oesophagus
Jianping Kong;
Jianping Kong
1Division of Gastroenterology, Department of Medicine, University of Pennsylvania, 415 Curie Boulevard, Philadelphia, PA 19104, U.S.A.
Search for other works by this author on:
Douglas B. Stairs;
Douglas B. Stairs
1Division of Gastroenterology, Department of Medicine, University of Pennsylvania, 415 Curie Boulevard, Philadelphia, PA 19104, U.S.A.
Search for other works by this author on:
John P. Lynch
John P. Lynch
1
1Division of Gastroenterology, Department of Medicine, University of Pennsylvania, 415 Curie Boulevard, Philadelphia, PA 19104, U.S.A.
1To whom correspondence should be addressed (email lynchj@mail.med.upenn.edu).
Search for other works by this author on:
Biochem Soc Trans (2010) 38 (2): 321–326.
Article history
Received:
September 08 2009
Citation
Jianping Kong, Douglas B. Stairs, John P. Lynch; Modelling Barrett's oesophagus. Biochem Soc Trans 1 April 2010; 38 (2): 321–326. doi: https://doi.org/10.1042/BST0380321
Download citation file:
Sign in
Don't already have an account? Register
Sign in to your personal account
You could not be signed in. Please check your email address / username and password and try again.
Could not validate captcha. Please try again.