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 peptide gastrin has been shown to have growth stimulatory effects on normal as well as malignant gastrointestinal tissue. In this study, we have examined the possibility of autocrine growth-stimulation of cultured colon tumor cells by a gastrin-like peptide. The gastrin/CCK receptor antagonist dibutyryl cGMP inhibited the proliferation of two human colon carcinoma cell lines HCT 116 (EC50 = 1.3 mM) and CBS (EC50 = 2.5 mM) in a dose-dependent manner. Marked morphological changes were observed in HCT 116 cells after treatment with 1 mM dibutyryl cGMP. In receptor binding assays, dibutyryl cGMP competed with 125I-labeled gastrin for binding to HCT 116 cells (IC50 = 1.8 mM). Another derivative of cyclic GMP, 8-Bromo cGMP used as control due to its considerably weaker affinity for the gastrin/CCK receptor, did not compete with radiolabeled gastrin for binding to HCT 116 cells and had no effect on the morphology or proliferation in monolayer cultures of HCT 116 or CBS cells at concentrations up to 10 mM. Antigastrin/CCK antisera was also found to have dose-dependent cytostatic effects on HCT 116 and CBS cells adapted to growth in serum-free medium. The antiproliferative effect of the gastrin/CCK receptor antagonist and antigastrin/CCK antibodies suggested that a gastrin-like peptide secreted by these cells may promote growth. Radioimmunoassay of the conditioned medium of these two cell lines indicated the presence of a gastrin-like peptide (10-50 pg/10(6) cells/72 h). Northern analysis using an oligonucleotide DNA probe complementary to the nucleotide sequence coding the dodecapeptide carboxyl terminal of human gastrin showed three transcripts (0.7, 3.3, and 3.7 kb) that hybridized with the probe. These data provide, for the first time, evidence for an autocrine growth stimulatory role of a gastrin/CCK-like peptide in cultured colon tumor cells.
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PMID:Evidence for autocrine growth stimulation of cultured colon tumor cells by a gastrin/cholecystokinin-like peptide. 229 33

The gastrin receptor is expressed in various human cancers, such as the adenocarcinoma of the colon. The peptide hormone gastrin and the C-terminal peptides derived from it act as growth factors for these cancers. The hypothesis for the present work was to use the gastrin receptor as a target for appropriately constructed cytotoxic agents. We developed methods to link tetragastrin and pentagastrin by their N-termini to cytotoxic 1-(2-chloroethyl)-3-benzyl-3-succinoyltriazene. These compounds, CBS-4 and CBS-5, respectively, whose complete structures were determined by multinuclear NMR and mass spectrometry, competed effectively with gastrin in an assay using either guinea pig stomach fundus or the rat acinar tumor cell line AR42J as the source of the receptor. CBS-5 was cytotoxic to AR42J cells but was not toxic to A549 human lung cancer cells, which do not express the receptor.
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PMID:Peptide-linked 1,3-dialkyl-3-acyltriazenes: gastrin receptor directed antineoplastic alkylating agents. 796 39