The decreased expression of Beclin-1 correlates with progression to esophageal adenocarcinoma: The role of deoxycholic acid

Heather B. Roesly, Mohammad R. Khan, Hwu Dau Rw Chen, Kimberly A. Hill, Nirushan Narendran, George S Watts, Xiaoxin Chen, Katerina Dvorak

Research output: Contribution to journalArticle

28 Citations (Scopus)

Abstract

Beclin-1 has a central role in the regulation of autophagy. Barrett's esophagus (BE) is associated with a significantly increased risk for the development of esophageal adenocarcinoma (EAC). In the current study, we evaluated the role of Beclin-1 and autophagy in the EAC. Biopsies obtained from patients with BE and EAC, tissues from a rat model of BE and EAC, and esophageal cell lines were evaluated for the expression of Beclin-1 by immunohistochemistry, immunoblotting, or RT-PCR. Since reflux of bile acids is important in EAC, we also evaluated the effect of exposure to deoxycholic acid (DCA) on autophagy and Beclin-1 expression. Beclin-1 expression was high in squamous epithelium and nondysplastic BE, whereas its expression was low in dysplastic BE and EAC. The same pattern of expression was observed in rat tissues and in esophageal cell lines. Normal esophageal epithelium and HET-1A cells (derived from normal squamous epithelium) show high levels of Beclin-1, but lower levels of Beclin-1 were found in BE and EAC cell lines (CP-A, CP-C, and OE33). Acute exposure to DCA led to increased Beclin-1 expression and increased autophagy as evaluated by electron microscopy and counting percentage of GFP-LC3positive BE cells with punctate pattern. In contrast, chronic exposure to DCA did not result in the alteration of Beclin-1 levels or autophagy. In summary, these data suggest that autophagy is initially activated in response to bile acids, but chronic exposure to bile acids leads to decreased Beclin-1 expression and autophagy resistance.

Original languageEnglish (US)
JournalAmerican Journal of Physiology - Gastrointestinal and Liver Physiology
Volume302
Issue number8
DOIs
StatePublished - Apr 15 2012

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Deoxycholic Acid
Barrett Esophagus
Adenocarcinoma
Autophagy
Bile Acids and Salts
Epithelium
Cell Line
Beclin-1
Immunoblotting
Electron Microscopy
Immunohistochemistry
Biopsy
Polymerase Chain Reaction

Keywords

  • Autophagy
  • Bile acids

ASJC Scopus subject areas

  • Gastroenterology
  • Physiology (medical)
  • Physiology
  • Hepatology

Cite this

The decreased expression of Beclin-1 correlates with progression to esophageal adenocarcinoma : The role of deoxycholic acid. / Roesly, Heather B.; Khan, Mohammad R.; Chen, Hwu Dau Rw; Hill, Kimberly A.; Narendran, Nirushan; Watts, George S; Chen, Xiaoxin; Dvorak, Katerina.

In: American Journal of Physiology - Gastrointestinal and Liver Physiology, Vol. 302, No. 8, 15.04.2012.

Research output: Contribution to journalArticle

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