Transcription Regulation of Human and Porcine Pepsinogen A
The gene regulation of pepsinogens is scientifically interesting, because of the high specificity of expression in gastric chief cells. Also from a clinical point of view pepsinogen gene regulation is interesting. Pepsinogen, activated by acid to pepsin, is one of the aggressive factors in the stomach that play a role in peptic ulcer disease (1). A dominantly inherited high pepsinogen A (PGA) output is associated with duodenal ulcer (2). On the other hand, a low production of pepsinogen A appears to be associated with atrophic gastritis and gastric cancer (3). Changes in gene expression of different isozymogens have been demonstrated in Barrett’s oesophagus (4) and gastric cancer (5). Defize et al. (6) showed, that these changes in gene expression may be associated with methylation of DNA. They demonstrated that N-methyl-N’nitro-N-nitrosoguanidine (MNNG), a methylating agent, caused changes in pepsinogen C (PGC) gene expression in rats and in PGA gene expression in cultured human gastric chief cells. In rats the changes in PGC expression were associated with the development of gastric cancer. Other studies have shown hypomethylation of the pepsinogen genes in pepsinogen producing tissue, i.e. fundic mucosa (7,8). A decrease of PG synthesis in gastric tumours was correlated with a different methylation pattern (9).
KeywordsPromoter Fragment Chief Cell Fundic Mucosa Methylation Sensitive Restriction Enzyme Transient Expression Analysis
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