title: Math1/Atoh1 contributes to intestinalization of esophageal keratinocytes by inducing the expression of Muc2 and Keratin-20.
abstract: BACKGROUND
  Esophageal intestinal metaplasia, also known as Barrett's esophagus, is the replacement of the normal epithelium with one that resembles the intestine morphologically. Generally, this includes intestinal mucin-secreting goblet cells. Barrett's esophagus is an important risk factor for adenocarcinoma development. In-vitro models for Barrett's esophagus have not, to date, focused on the induction of goblet cells in Barrett's epithelium.
  
  
  OBJECTIVE
  To explore the contribution of Math1/Atoh1 to induction of Barrett's esophagus and intestinal mucin-secreting goblet cells from normal human esophageal epithelium.
  
  
  METHODS
  We explored the level and pattern of Math1/Atoh1 mRNA and protein expression in human Barrett's esophagus. Then, using retroviral-mediated gene expression, we induced Math1 mRNA and protein expression in a human esophageal keratinocyte cell line. We evaluated the effects of this ectopic Math1 expression on cell proliferation and gene expression patterns in cells cultured under two-dimensional and three-dimensional tissue-engineering conditions.
  
  
  RESULTS
  Math1/Atoh1 mRNA and protein are detected in human Barrett's esophagus specimens, but the mRNA levels vary substantially. In the keratinocyte expression studies, we observed that Math1/Atoh1 ectopic expression significantly reduced cell proliferation and altered cell morphology. Moreover, Math1/Atoh1 expression is associated with a more intestinalized gene expression pattern that is distinct from that reported in after studies using other intestinal transcription factors. Most significantly, we observe the induction of the Barrett's esophagus markers Mucin-2 and Keratin-20 with Math1/Atoh1 expression.
  
  
  CONCLUSIONS
  We conclude that ectopic Math1/Atoh1 expression makes unique contributions to intestinalization of the esophageal epithelium in Barrett's esophagus.
authors.affiliation: Department of Medicine, Division of Gastroenterology, University of Pennsylvania, 650 CRB 415 Curie Blvd., Philadelphia, PA 19104, USA.
authors.forename: Jianping
authors.initials: J
authors.lastname: Kong
authors.forename: Mary Ann S
authors.initials: MA
authors.lastname: Crissey
authors.forename: Antonia R
authors.initials: AR
authors.lastname: Sepulveda
authors.forename: John P
authors.initials: JP
authors.lastname: Lynch
mesh_terms: D001471:Barrett Esophagus / Q000235:genetics / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology*; D051792:Basic Helix-Loop-Helix Proteins / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D002454:Cell Differentiation; D002460:Cell Line; D049109:Cell Proliferation; D002478:Cells, Cultured; D046508:Culture Techniques; D004947:Esophagus / Q000473:pathology*; D015870:Gene Expression; D020397:Goblet Cells / Q000378:metabolism / Q000473:pathology; D006801:Humans; D053554:Keratin-20 / Q000235:genetics / Q000378:metabolism*; D015603:Keratinocytes / Q000378:metabolism*; D055262:Mucin-2 / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism
chemical_list: D051792:Basic Helix-Loop-Helix Proteins; D053554:Keratin-20; D055262:Mucin-2; D012333:RNA, Messenger; C500942:ATOH1 protein, human