Abstract
The G protein-coupled human gastrin-releasing peptide receptor (hGRP-R) is frequently found aberrantly expressed in human cancers of the colon, stomach, and lung, and its ligand-specific activation has been implicated in cell proliferation and differentiation. Here, we demonstrated hGRP-R activation stimulated sustained cyclic AMP response element binding protein (CREB) phosphorylation and transactivation in duodenal cancer cells through a protein kinase C and partially p38 mitogen-activated protein kinase-dependent pathway. In contrast, intracellular calcium, ERK1/2, protein kinase A, and PI3 kinase were not involved. This novel signaling mechanism might be of importance for regulation of CREB-dependent gene expression in human cancer expressing functional hGRP-R.
Publication types
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Bombesin / pharmacology
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Calcium / metabolism
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Cyclic AMP Response Element-Binding Protein / drug effects
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Cyclic AMP Response Element-Binding Protein / genetics
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Cyclic AMP Response Element-Binding Protein / metabolism*
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Cyclic AMP-Dependent Protein Kinases / metabolism
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Duodenal Neoplasms / metabolism*
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Enzyme Inhibitors / pharmacology
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Humans
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Imidazoles / pharmacology
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Mitogen-Activated Protein Kinase 1 / metabolism
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Mitogen-Activated Protein Kinase 3
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Mitogen-Activated Protein Kinases / antagonists & inhibitors
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Mitogen-Activated Protein Kinases / metabolism
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Phosphorylation / drug effects
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Protein Kinase C / metabolism
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Pyridines / pharmacology
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Receptors, Bombesin / metabolism*
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Recombinant Fusion Proteins / drug effects
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Recombinant Fusion Proteins / genetics
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Recombinant Fusion Proteins / metabolism
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Serine / metabolism
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Transcription, Genetic
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Transcriptional Activation*
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Tumor Cells, Cultured
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p38 Mitogen-Activated Protein Kinases
Substances
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Cyclic AMP Response Element-Binding Protein
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Enzyme Inhibitors
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Imidazoles
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Pyridines
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Receptors, Bombesin
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Recombinant Fusion Proteins
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Serine
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Cyclic AMP-Dependent Protein Kinases
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Protein Kinase C
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Mitogen-Activated Protein Kinase 1
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Mitogen-Activated Protein Kinase 3
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Mitogen-Activated Protein Kinases
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p38 Mitogen-Activated Protein Kinases
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SB 203580
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Bombesin
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Calcium