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Title: | Gastrin increases its own synthesis in gastrointestinal cancer cells via the CCK2 receptor. | Austin Authors: | Kovac, Suzana;Xiao, Lin;Shulkes, Arthur;Patel, Oneel;Baldwin, Graham S | Affiliation: | The University of Melbourne, Department of Surgery, Austin Health, Heidelberg, Victoria, Australia | Issue Date: | 8-Oct-2010 | Publication information: | Febs Letters 2010; 584(21): 4413-8 | 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. | Gov't Doc #: | 20932834 | URI: | https://ahro.austin.org.au/austinjspui/handle/1/11133 | DOI: | 10.1016/j.febslet.2010.09.046 | Journal: | FEBS letters | URL: | https://pubmed.ncbi.nlm.nih.gov/20932834 | Type: | Journal Article | Subjects: | Base Sequence Cell Line, Tumor Colorectal Neoplasms.blood.genetics.metabolism Feedback, Physiological Gastrins.biosynthesis.blood.genetics.metabolism Gastrointestinal Neoplasms.genetics.metabolism.pathology Gene Expression Regulation, Neoplastic Genes, Reporter.genetics Humans Luciferases.genetics MAP Kinase Signaling System Molecular Sequence Data Polymerase Chain Reaction Promoter Regions, Genetic.genetics Receptor, Cholecystokinin B.metabolism Time Factors Transcription, Genetic Transcriptional Activation |
Appears in Collections: | Journal articles |
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