The trefoil peptide TFF1 inhibits the growth of the human gastric adenocarcinoma cell line AGS.

TFF1 is a 60-amino acid peptide produced in normal gastric mucosa which forms dimers spontaneously. Tumours of patients with gastric cancer usually have reduced TFF1 levels and disruption of the TFF1 gene causes animals to develop gastric adenomas and carcinomas. The effect of normal sequence human recombinant TFF1 and an analogue (Cys(58)-->Ser(58)), which is unable to dimerize, on the proliferation and morphology of the human gastric adenocarcinoma cell line AGS was therefore investigated. Proliferation, assessed by total cell number and [methyl-(3)H]thymidine incorporation, was reduced by dimeric TFF1 in a dose-dependent manner. Monomeric TFF1 also reduced proliferation but was less potent than the dimeric form. It is concluded that TFF1 may be an important controller of gastric cell proliferation, that dimerization of TFF1 is important in this effect, and that the reduced levels of TFF1 seen in gastric cancer may be of clinical relevance.