Expressional profiles of transcription factors in the progression of Helicobacter pylori-associated gastric carcinoma based on protein/DNA array analysis
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Transcription factors (TFs) are crucial modulators of gene expression during the development and progression of gastric carcinoma. Helicobacter pylori (H. pylori) is one of the most significant risk factors of gastric carcinoma, and it is widely known that chronic inflammation with H. pylori infection triggers gastric carcinogenesis through inflammation-carcinoma chain [gastric carcinogenesis stages: non-atrophic gastritis, chronic atrophic gastritis, intestinal metaplasia, dysplasia and gastric carcinoma (GC)], but its mechanism regarding changed TFs remains unknown. In this study, we investigated the expressional profiles of 345 transcription factors in gastric mucosa of healthy volunteers and patients at different gastric carcinogenesis stages using protein/DNA array-based approach. The data demonstrated the up-regulated TFs such as GATA-3, AP4, c-Myc and Pbx1 in the gastric mucosa of GC patients compared with the healthy volunteers, while other TFs, particularly CCAAT and CACC, showed the consistently decreasing trend along the gastric carcinogenesis. The increased expressions of AP4, Pbx1 and C/EBPα were further validated by quantitative real-time PCR and Western blot in various H. pylori-infected models such as clinical gastric tissues, gastric epithelial cell lines and Mongolian gerbils. This study provides insights into and potential laws for gene transcriptional regulation by identifying potential TFs targets against the development of H. pylori-associated gastric carcinoma.
KeywordsTranscription factors Helicobacter pylori Gastric carcinogenesis Protein/DNA array analysis AP4 Pbx1 C/EBPα
- H. pylori
Normal gastric mucosa
Chronic atrophic gastritis
Precancerous lesions of gastric cancer
Cytotoxin-associated gene A
Vacuolating cytotoxin gene A
GATA-binding protein 3
Activator protein 4 binding element
Pre-B-cell leukemia transcription factor 1
- C/EBP α
CCAAT/enhancer-binding protein α
This study is supported by a Grant from the National Natural Science Foundation of China (No. 81172301).
Hu T analyzed the data and wrote the manuscript; Huang L guided the analysis and manuscript writing; Xu CX designed the study, performed the endoscopic procedures, collected specimens and revised the manuscript; Liu X, Xiao J and Zhou L conducted the cell and Helicobacter pylori experiments; Wang Y collected and sent the specimens for array analysis; Luo L and Jiang X performed the experiment of Mongolian gerbils.
Compliance with ethical standards
Conflict of interest
All authors declare that they have no conflict of interest.
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