Journal Article

Overexpression of glucose-regulated protein 94 (Grp94) in esophageal adenocarcinomas of a rat surgical model and humans

Xiaoxin Chen, Yu Ding, Chang-Gong Liu, Samer Mikhail and Chung S. Yang

in Carcinogenesis

Volume 23, issue 1, pages 123-130
Published in print January 2002 | ISSN: 0143-3334
Published online January 2002 | e-ISSN: 1460-2180 | DOI: http://dx.doi.org/10.1093/carcin/23.1.123
Overexpression of glucose-regulated protein 94 (Grp94) in esophageal adenocarcinomas of a rat surgical model and humans

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A rat surgical esophageal adenocarcinoma (EAC) model induced by esophagogastroduodenal anastomosis was recently established in our laboratory. This model mimics mixed reflux of gastric and duodenal contents in human patients and produces EAC without treatment with any carcinogen. We compared the protein expression pattern between rat EAC and normal tissues by 2-dimensional protein gel electrophoresis. The overexpressed protein spots of the tumor sample were cut out and analyzed by matrix-assisted laser desorption/ionization mass spectrometry. Several stress proteins (Grp94, Grp78, calnexin, Hsp90β and ER61) were identified by this method. Western blotting and RT–PCR further confirmed overexpression of Grp94 in rat EAC. Immunohistochemical staining also revealed expression of Grp94 in the epithelial cells of columnar lined esophagus and EAC. Similar to the rat model, well-differentiated human EAC and gastric cardia adenocarcinomas were also found to overexpress Grp94, but esophageal squamous cell carcinomas did not. We also characterized apoptosis, cell proliferation and oxidative DNA damage in the rat tissues. Since Grp94 is known to inhibit apoptosis by maintaining intracellular Ca2+ homeostasis, our data suggest a possible correlation between oxidative stress, Grp94 overexpression and apoptosis regulation in esophageal adenocarcinogenesis.

Keywords: BrdU, bromodeoxyuridine; CLE, columnar lined esophagus; 2-DE, two-dimensional gel electrophoresis; 2′-dG, 2′-deoxyguanosine; EAC, esophageal adenocarcinoma; EGDA, esophagogastroduodenal anastomosis; Grp94, glucose-regulated protein 94; MALDI-MS, matrix-assisted laser desorption/ionization mass spectrometry; 8-OHdG, 8-hydroxydeoxyguanosine; PBS, phosphate-buffered saline.

Journal Article.  4679 words.  Illustrated.

Subjects: Clinical Cytogenetics and Molecular Genetics

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