Overexpression of glucose-regulated protein 94 (Grp94) in esophageal adenocarcinomas of a rat surgical model and humans.
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, Hsp90beta 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 Ca(2+) homeostasis, our data suggest a possible correlation between oxidative stress, Grp94 overexpression and apoptosis regulation in esophageal adenocarcinogenesis.
Chen
Xiaoxin
X
Laboratory for Cancer Research, College of Pharmacy, Rutgers-State University of New Jersey, 164 Frelinghuysen Road, Piscataway, NJ 08854, USA.
Ding
Yu
Y
Liu
Chang-Gong
CG
Mikhail
Samer
S
Yang
Chung S
CS
D000230:Adenocarcinoma / Q000378:metabolism* / Q000473:pathology / Q000601:surgery; D000714:Anastomosis, Surgical; D000818:Animals; D017209:Apoptosis; D015153:Blotting, Western; D002455:Cell Division; D004249:DNA Damage; D004195:Disease Models, Animal; D004379:Duodenal Neoplasms / Q000378:metabolism / Q000473:pathology / Q000601:surgery; D015180:Electrophoresis, Gel, Two-Dimensional; D000091342:Endoplasmic Reticulum Chaperone BiP; D004938:Esophageal Neoplasms / Q000378:metabolism* / Q000473:pathology / Q000601:surgery; D004947:Esophagus / Q000473:pathology / Q000601:surgery; D018840:HSP70 Heat-Shock Proteins / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D006801:Humans; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D008565:Membrane Proteins / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D018384:Oxidative Stress; D012333:RNA, Messenger / Q000032:analysis / Q000235:genetics; D051381:Rats; D020133:Reverse Transcriptase Polymerase Chain Reaction; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; D013274:Stomach Neoplasms / Q000378:metabolism / Q000473:pathology / Q000601:surgery
D000091342:Endoplasmic Reticulum Chaperone BiP; D018840:HSP70 Heat-Shock Proteins; C000717247:HSPA5 protein, human; D008565:Membrane Proteins; D012333:RNA, Messenger; C018551:glucose-regulated proteins