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Gastrin increases its own synthesis in gastrointestinal cancer cells via the CCK2 receptor
Author(s) -
Kovac Suzana,
Xiao Lin,
Shulkes Arthur,
Patel Oneel,
Baldwin Graham S.
Publication year - 2010
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/j.febslet.2010.09.046
Subject(s) - gastrin , transactivation , autocrine signalling , gastrointestinal hormone , receptor , gastrointestinal cancer , cancer research , hormone , medicine , endocrinology , colorectal cancer , epidermal growth factor receptor , cancer , biology , peptide hormone , chemistry , transcription factor , secretion , biochemistry , gene
The involvement of the gastrointestinal hormone gastrin in the development of gastrointestinal cancer is highly controversial. Here we demonstrate a positive‐feedback loop whereby gastrin, acting via the CCK2 receptor, increases its own expression. Such an autocrine loop has not previously been reported for any other gastrointestinal hormone. Gastrin promoter activation was dependent on the MAP kinase pathway and did not involve Sp1 binding sites or epidermal growth factor receptor transactivation. As the treatment of gastrointestinal cancer cells with amidated gastrin led to increased expression of non‐amidated gastrins, the positive‐feedback loop may contribute to the sustained increase in circulating gastrins observed in colorectal cancer patients.