Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P01350 (gastrin)
 9,683 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The rat pancreatic carcinoma cell line AR4-2J was screened for growth-associated genes linked to the mitogenic effect of the novel gut brain hormone, pituitary adenylate cyclase activating polypeptide (PACAP). Using the mRNA differential display technique, we identified and sequenced an unknown rat gene, PACAP-responsive gene 1 (PRG1), which is highly homologous to gly96, a novel murine gene of unknown function. The PRG1 cDNA sequence of 1.1 kb encodes a 160-amino acid protein. Using targeted PCR, the gene structure of PRG1, constituting 0.6 kb of the promotor region, and the DNA coding region, including a single 107-bp intron, were established from rat genomic DNA. In AR4-2J cells, PACAP(1-38) increased PRG1 mRNA levels up to 10-fold in a rapid (30 min), transient (3-6 h), and dose-dependent (ED50, <1 nM) fashion. The growth-stimulating gastrointestinal hormones cholecystokinin and gastrin showed a similar degree of PRG1 induction, and the PACAP-related peptides vasoactive intestinal peptide and secretin were without effect. The transcriptional inhibitor actinomycin D, various protein kinase C inhibitors, and the calmodulin inhibitor W-7 strongly reduced PRG1 induction by PACAP, whereas the translational inhibitor cycloheximide potently increased PRG1 mRNA levels in unstimulated and PACAP-stimulated cells. Feedback-mediated hyperplasia of the rat exocrine pancreas induced by oral treatment of rats with the protease inhibitor camostate (FOY-305) was preceded by a 15-fold transient elevation of PRG1 mRNA levels. These data suggest that PRG1 is an early-response gene linked to PACAP-induced growth of AR4-2J cells as well as to hyperplasia of the rat exocrine pancreas in vivo.
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PMID:PRG1: a novel early-response gene transcriptionally induced by pituitary adenylate cyclase activating polypeptide in a pancreatic carcinoma cell line. 865 10

Addressing the puzzling role of amidated gastrin(17) (G17) and the gastrin/CCKB/CCK2 receptor in colorectal carcinogenesis, we analysed potential candidate genes involved in G17-dependent NF-kappaB inhibition and apoptosis. The colorectal carcinoma cell line Colo320 overexpressing the wild-type CCK2 receptor (Colo320wt) underwent G17-induced apoptosis along with suppressed NF-kappaB activation and decreased expression of the antiapoptotic NF-kappaB target genes cIAP1 and cIAP2, whereas G17 was without effect on Colo320 cells expressing a CCK2 receptor bearing a loss of function mutation (Colo320mut). Gene microarray analysis revealed an elevated expression of the stress response gene IEX-1 in G17-treated Colo320wt but not Colo320mut cells. Quantitative real-time PCR and conventional RT-PCR confirmed this G17-dependent increase of IEX-1 expression in Colo320wt cells. If these cells were subjected to IEX-1 knockdown by small interfering RNA transfection, the apoptosis-inducing effect of G17 was abolished. Moreover, tumor necrosis factor alpha (TNFalpha)- or 5-FU-induced apoptosis that is greatly enhanced by G17 treatment in Colo320wt cells was prevented if IEX-1 expression was repressed. Under these conditions of blocked IEX-1 expression, the NF-kappaB activity remained unaffected by G17, in particular in Colo320wt cells co-treated with TNFalpha and also the suppressive effect of G17 on cIAP1 and cIAP2 expression was not observed anymore if IEX-1 expression was blocked. Conversely, IEX-1 overexpression in Colo320mut cells caused an increase of basal and TNFalpha- or 5-FU-induced apoptosis, an effect not further triggered by G17 treatment. Using a xenograft tumor model in severe combined immune deficiency mice, we could show that experimental systemic hypergastrinemia induced by the administration of omeprazole led to enhanced apoptosis as well as to a marked increase of IEX-1 expression in Colo320wt tumors, but not in Colo320mut tumors. These observations indicate that the proapoptotic effect of G17 on human colon cancer cells expressing the wild-type CCK2 receptor is mediated by IEX-1, which modulates NF-kappaB-dependent antiapoptotic protection and thereby exerts tumor-suppressive potential.
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PMID:The apoptosis-inducing effect of gastrin on colorectal cancer cells relates to an increased IEX-1 expression mediating NF-kappa B inhibition. 1770 4