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Gastric cancer is the fourth most commonly diagnosed malignancy and thesecond leading cause of cancer-related mortality worldwide. Recent research suggeststhat tissue stem cells and the self renewal transcription factor, octamer-bindingtranscription factor 4 (Oct4), could be involved in the development of certaintumors. The aim of this study was to investigate the expression pattern of Oct4in normal human stomach and during multistep gastric carcinogenesis. Pyloric antralmucosal tissues were obtained from consenting individuals undergoing endoscopy(due to upper gastrointestinal symptoms) and gastrectomy (due to pyloric antraladenocarcinoma). Some tissue samples were processed to assemble an array of tissuesections representing multistep carcinogenesis and probed using anti-Oct4 antibodiesand lectins specific for α-L-fucose or N-acetyl-D-glucosamine. Some tissue sampleswere processed for subcellular fractionation and western blot analysis using thesame antibodies. The results revealed that Oct4-expressing cells were found inthe proliferative cell compartment of the pit-gland units of microscopically normalgastric mucosal biopsies. Mucosal tissues with evidence of severe gastritis, metaplastic/dysplastictransformation and gastric cancer showed a significant increase in the expressionof Oct4 (the labeled area increased from 2% in the control to 6 and 16% in thegastritis and cancerous tissues, respectively), suggesting a role for Oct4 inthe early stages of cancer development. Furthermore, the data revealed an alterationin the subcellular distribution of Oct4, possibly due to the inhibition of cytoplasm-to-nucleustranslocation during carcinogenesis. In conclusion, this study demonstrates analteration in the expression pattern and nuclear translocation of Oct4 duringgastric carcinogenesis and may be helpful in designing new modalities for theearly detection and/or therapy of gastric cancer.

Upregulation and inhibition of the nuclear translocation of Oct4 during multistep gastric carcinogenesis