Gastrin increases its own synthesis in gastrointestinal cancer cells via the CCK2 receptor

Autor: Graham S. Baldwin, Oneel Patel, Arthur Shulkes, Suzana Kovac, Lin Xiao
Rok vydání: 2010
Předmět:
Transcriptional Activation
medicine.medical_specialty
Time Factors
Transcription
Genetic
MAP Kinase Signaling System
medicine.medical_treatment
Molecular Sequence Data
Biophysics
Polymerase Chain Reaction
digestive system
Biochemistry
Hypergastrinemia
Transactivation
Genes
Reporter
Structural Biology
Cell Line
Tumor
Internal medicine
Gastrins
Genetics
medicine
Humans
Gastrointestinal cancer
Epidermal growth factor receptor
Luciferases
Promoter Regions
Genetic
Receptor
Autocrine signalling
Molecular Biology
Gastrointestinal Neoplasms
Gastrin
Feedback
Physiological
Base Sequence
biology
Growth factor
digestive
oral
and skin physiology
Cell Biology
medicine.disease
Colorectal cancer
Receptor
Cholecystokinin B
Gene Expression Regulation
Neoplastic
Endocrinology
Gastrointestinal hormone
biology.protein
Colorectal Neoplasms
hormones
hormone substitutes
and hormone antagonists
Zdroj: FEBS Letters. 584:4413-4418
ISSN: 0014-5793
DOI: 10.1016/j.febslet.2010.09.046
Popis: 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.
Databáze: OpenAIRE
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