Gastrin increases its own synthesis in gastrointestinal cancer cells via the CCK2 receptor |
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Authors: | Kovac Suzana Xiao Lin Shulkes Arthur Patel Oneel Baldwin Graham S |
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Institution: | The University of Melbourne, Department of Surgery, Austin Health, Heidelberg, Victoria, Australia |
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Abstract: | 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. |
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Keywords: | CCK2R cholecystokinin-2 receptor EGFR epidermal growth factor receptor CRC colorectal cancer Luc luciferase MAPK mitogen activated protein kinase |
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