Proteomic Screening of a Cell Line Model of Esophageal Carcinogenesis Identifies Cathepsin D and Aldo-Keto Reductase 1C2 and 1B10 Dysregulation in Barrett’s Esophagus and Esophageal Adenocarcin

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• 作者：Jean Breton ; Matthew C. Gage ; Alastair W. Hay ; Jeffrey N. Keen ; Christopher P. Wild ; Clare Donnellan ; John B. C. Findlay ; Laura J. Hardie
• 刊名：Journal of Proteome Research
• 出版年：2008
• 出版时间：May 2008
• 年：2008
• 卷：7
• 期：5
• 页码：1953 - 1962
• 全文大小：3053K
• 年卷期：v.7,no.5(May 2008)
• ISSN：1535-3907

文摘

Esophageal adenocarcinoma (EA) incidence is increasing rapidly and is associated with a poor prognosis. Identifying biomarkers of disease development and progression would be invaluable tools to inform clinical practice. Two-dimensional polyacrylamide gel electrophoresis was used to screen 10 esophageal cell lines representing distinct stages in the development of esophageal cancer. Thirty-three proteins were identified by MALDI-TOF-MS which demonstrated differences in expression across the cell lines. Western blotting and qRT-PCR confirmed increased cathepsin D and aldo-keto reductases 1C2 and 1B10 expression in metaplastic and dysplastic cell lines. Expression of these proteins was further assessed in esophageal epithelium from patients with nonerosive (NERD) and erosive gastro-esophageal reflux disease, Barrett’s esophagus (BE) and EA. When compared with normal epithelium of NERD patients, (i) cathepsin D mRNA levels demonstrated a stepwise increase in expression (p < 0.05) in erosive, metaplastic and EA tissue; (ii) AKR1B10 expression increased (p < 0.05) 3- and 9-fold in erosive and Barrett’s epithelium, respectively; and (iii) AKR1C2 levels increased (p < 0.05) in erosive and Barrett’s epithelium, but were reduced (p < 0.05) in EA. These proteins may contribute to disease development via effects on apoptosis, transport of bile acids and retinoid metabolism and should be considered as candidates for further mechanistic and clinical investigations.