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

The effect of a long-acting somatostatin analogue SMS 201.995 (SMS; Sandoz) on basal and gastrin-stimulated growth of 4 human colon cancer lines was studied in vitro and in vivo. Proliferation assay was done with overnight [75Se]selenomethionine uptake after 5 days of incubation. Gastrin concentrations used were 5e-10 M and 1e-7 M. SMS concentrations were from 2e-12 M to 2e-7 M. Cell lines LIM 1215, LIM 2405, and LIM 2412 were inhibited dose-dependently in both basal and gastrin-stimulated groups. LIM 1863 was slightly stimulated. Based on in vivo growth characteristics, LIM 2412 and LIM 2405 were selected for xenograft study. The dose of 50 micrograms/kg/day was arrived at after a preliminary experiment showed it to be safe and effective. The LIM 2412 xenografts in the SMS-treated animals were 473.3 +/- 99.9 (SD) versus 838.1 +/- 111.3 mm3 in control (P less than 0.05) after 20 days. The LIM 2405 tumors were also significantly inhibited (81.2 +/- 30.0 versus 245.7 +/- 48.3 mm3, P less than 0.01). The effect of SMS appeared to be reversible. Oral SMS at 200 micrograms/kg/day was not absorbed. This study suggests that SMS may have direct antitumor effects in human colon cancer.
 ...
PMID:SMS 201.995 inhibits in vitro and in vivo growth of human colon cancer. 173 55

The hypothesis that a gastrin-like peptide is acting as an autocrine growth factor in gastric and colonic carcinoma cell lines requires that the cells should synthesize a gastrin-like mRNA. Although no gastrin mRNA was observed in the gastric line Okajima or the colonic lines HCT 116 or LIM 1215 by Northern blotting, gastrin mRNA was detected by application of the polymerase chain reaction. Two products were observed corresponding to mRNA with and without a 130 bp intron. The sequences of both products were identical to the sequences predicted from the normal human gastrin gene.
 ...
PMID:PCR cloning and sequence of gastrin mRNA from carcinoma cell lines. 238 63

The nucleotide sequence encoding the human 78 kDa gastrin binding protein (GBP) has been deduced from overlapping fragments generated by the polymerase chain reaction with oligonucleotides based on the sequence of the porcine GBP (Mantamadiotis, T. et al. (1993) Biochim. Biophys. Acta 1170, 211-215) and cDNA from the colonic carcinoma cell line LIM 1215 as template. The mature human GBP is 90% identical to the porcine GBP. Clones encoding the human GBP gene, which contains 19 exons, have been isolated from human genomic libraries. The positions of the exon/intron junctions are completely different from the junctions in the gene encoding the related peroxisomal trifunctional enzyme. Clones encoding a related pseudogene have also been isolated and sequenced.
 ...
PMID:Structures of the human cDNA and gene encoding the 78 kDa gastrin-binding protein and of a related pseudogene. 791 61

To assess the potential of gastrin receptor antagonists in the treatment of gastrointestinal cancer, the presence of an autocrine loop involving progastrin-derived peptides has been investigated in two colorectal and one gastric carcinoma cell lines. Progastrin, glycine-extended gastrin and amidated gastrin were detected in cell extracts or conditioned media by radio-immunoassay. Low-affinity binding sites for glycine-extended gastrin and amidated gastrin were present, but high-affinity binding sites were not detected with the appropriate iodinated ligands. In addition, neither glycine-extended gastrin nor amidated gastrin in the concentration range 10pmol/L-10nmol/L stimulated cell proliferation. We conclude that it is unlikely that the carcinoma cell lines LIM 1215, LIM 1839 and LIM 1899 use either amidated or glycine-extended gastrins as extracellular autocrine growth factors.
 ...
PMID:Expression of progastrin-derived peptides and gastrin receptors in a panel of gastrointestinal carcinoma cell lines. 1022 25

The three subtypes of peroxisome proliferator activated-receptors (PPARalpha, delta and gamma) control the storage and metabolism of fatty acids. Treatment of rats with the PPARalpha ligand ciprofibrate increases serum gastrin concentrations, and several lines of evidence suggest that non-amidated gastrins act as growth factors for the colonic mucosa. The aim of the present study was to investigate the expression of PPARs and the effect of PPAR ligands on gastrin production and cell proliferation in human colorectal carcinoma (CRC) cell lines. mRNAs for all three PPAR subtypes were detected by PCR in all CRC cell lines tested. The concentrations of progastrin, but not of glycine-extended or amidated gastrin, measured by radioimmunoassay in LIM 1899 conditioned media and cell extracts were significantly increased by treatment with the PPARalpha ligand clofibrate. Similar increases in progastrin were seen following treatment with the PPARalpha ligands ciprofibrate and fenofibrate, but not with bezafibrate, gemfibrozil or Wy 14643. The PPARgamma agonist rosiglitazone had no significant effect on progastrin production. The PPARalpha ligand clofibrate also stimulated proliferation of the LIM 1899 cell line. We conclude that some PPARalpha ligands increase progastrin production by the human CRC cell line LIM 1899, and that clofibrate increases proliferation of LIM 1899 cells. These studies have revealed a relationship between PPARs and gastrin, two regulatory molecules implicated in the pathogenesis of CRC.
 ...
PMID:PPARalpha agonists stimulate progastrin production in human colorectal carcinoma cells. 1517 43

Previous studies demonstrated that mice with a null mutation in the gene encoding the hormone gastrin have impaired gastric acid secretion. Hence, the aim of this study was to evaluate changes in the acid-secreting parietal cell in gastrin-deficient (GAS-KO) mice. Analysis of several transcripts encoding parietal cell proteins involved in gastric acid secretion showed reduced abundance in the GAS-KO stomach, including H+,K+-ATPase alpha- and beta-subunits, KCNQ1 potassium channel, aquaporin-4 water channel, and creatine kinase B, which were reversed by gastrin infusion for 1 wk. Although mRNA and protein levels of LIM and SH3 domain-containing protein-1 (LASP-1) were not greatly changed in the mutant, there was a marked reduction in phosphorylation, consistent with its proposed role as a cAMP signal adaptor protein associated with acid secretion. A more comprehensive analysis of parietal cell gene expression in GAS-KO mice was performed using the Affymetrix U74AV2 chip with RNA from parietal cells purified by flow cytometry to >90%. Comparison of gene expression in GAS-KO and wild-type mice identified 47 transcripts that differed by greater than or equal to twofold, suggesting that gastrin affects parietal cell gene expression in a specific manner. The differentially expressed genes included several genes in signaling pathways, with a substantial number (20%) known to be target genes for Wnt and Myc.
 ...
PMID:Gene expression profiling of gastrin target genes in parietal cells. 1627 79