Review article: regulation of TFF1 (pS2) expression in gastric epithelial cells

Trefoil factor family (TFF) is a group of small peptides secreted by gastrointestinal epithelial cells.

Among three known TFF peptides, TFF1 (formerly pS2) is expressed at a high level in gastric epithelial cells and plays an essential and critical role in maintaining the integrity of the gastric mucosa. Recent evidence also suggests that TFF1 acts as a tumour suppressor gene in the stomach.

TFF1 was originally discovered as an oestrogen-inducible gene in MCF-7 breast cancer cells, and its expression is dependent on oestrogen in MCF-7 and other hormone-dependent breast cancer cells. Although gastric epithelial cells express oestrogen receptors (ERs), gastric TFF1 expression appears to be independent of oestrogen signalling. Instead, several cis-regulatory elements are involved in the regulation of gastric TFF1 expression and balanced signalling from gp130, a common IL-6 family coreceptor, has been shown to be necessary for the proper expression of TFF1 in the stomach.

Epigenetic regulation, such as DNA methylation in the promoter region of the TFF1 gene, may be also important for tissue-specific expression of TFF1 in the stomach. However, further studies are still needed to fully understand the detailed regulatory mechanisms of TFF1 expression in gastric epithelial cells.