|Title||The decreased expression of Beclin-1 correlates with progression to esophageal adenocarcinoma: the role of deoxycholic acid.|
|Publication Type||Journal Article|
|Year of Publication||2012|
|Authors||Roesly HB, Khan MR, Chen HDau Rw, Hill KA, Narendran N, Watts GS, Chen X, Dvorak K|
|Journal||Am J Physiol Gastrointest Liver Physiol|
|Date Published||2012 Apr 15|
|Keywords||Adenocarcinoma, Amino Acids, Animals, Apoptosis Regulatory Proteins, Autophagy, Barrett Esophagus, Beclin-1, Bile Acids and Salts, Blotting, Western, Cell Line, Tumor, Cell Proliferation, Deoxycholic Acid, Disease Progression, Esophageal Neoplasms, Humans, Immunohistochemistry, Membrane Proteins, Microarray Analysis, Microscopy, Confocal, Microscopy, Electron, Transmission, Rats, Real-Time Polymerase Chain Reaction, RNA, RNA, Small Interfering|
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-LC3-positive 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.
|Alternate Journal||Am. J. Physiol. Gastrointest. Liver Physiol.|
|PubMed Central ID||PMC3355563|
|Grant List||P30 CA023074 / CA / NCI NIH HHS / United States |
P30 ES006694 / ES / NIEHS NIH HHS / United States
CA-95060 / CA / NCI NIH HHS / United States
The decreased expression of Beclin-1 correlates with progression to esophageal adenocarcinoma: the role of deoxycholic acid.
Faculty Member Reference:
George Watts, Ph.D.