The decreased expression of Beclin-1 correlates with progression to esophageal adenocarcinoma: the role of deoxycholic acid
| Autor: | Kimberly A. Hill, Hwu Dau Rw Chen, Katerina Dvorak, Mohammad Rizwan Khan, Heather B. Roesly, George S. Watts, Xiaoxin Chen, Nirushan Narendran |
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| Rok vydání: | 2012 |
| Předmět: |
Pathology
medicine.medical_specialty Esophageal Neoplasms Physiology Blotting Western Adenocarcinoma Biology Real-Time Polymerase Chain Reaction Bile Acids and Salts Barrett Esophagus chemistry.chemical_compound Microscopy Electron Transmission Cell Line Tumor Physiology (medical) Autophagy medicine Animals Humans Amino Acids RNA Small Interfering Esophagus Cancer Biology Cell Proliferation Microscopy Confocal Hepatology Cell growth Deoxycholic acid Gastroenterology Membrane Proteins Microarray Analysis medicine.disease Immunohistochemistry Epithelium Rats Real-time polymerase chain reaction medicine.anatomical_structure chemistry Disease Progression Cancer research RNA Beclin-1 Apoptosis Regulatory Proteins Deoxycholic Acid |
| Zdroj: | American Journal of Physiology-Gastrointestinal and Liver Physiology. 302:G864-G872 |
| ISSN: | 1522-1547 0193-1857 |
| DOI: | 10.1152/ajpgi.00340.2011 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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