title: Gastrin 1-6 promotes growth of colon cancer cells through non-CCK receptors.
abstract: Our previous studies have shown that stimulation of proliferation of DLD-1 and HT29 human colonic cancer cells by nanomolar gastrin (G17) and carboxymethyl gastrin (G17Gly) and reversal of growth by micromolar G17 and G17Gly involves binding sites which can neither be CCK1 nor CCK2 receptors; the N terminal fragment, G17(1-12), is sufficient to increase the number of HT-29 cells by binding the higher affinity binding site but is without a suppressing effect through the lower affinity site. In this study with DLD-1 cells, competitive binding using 125I-G17(1-12) showed that G17(1-12) binds both high and low affinity sites, as do G17 and G17Gly. G17(1-6)-NH2, even without the central-to-C-terminal portion of G17, was still able to bind a single site and to promote a dose-dependent increase in cell number at nanomolar concentrations. The results indicate the presence of a non-CCK receptor on human colonic cancer cells which could mediate the tumor-promoting activity of the N-terminal-to-central portion of G17Gly which, unlike G17, is produced by such cells.
authors.affiliation: Department of Biomedical Sciences, Creighton University, Omaha, NE 68178, USA.
authors.forename: Jeffrey
authors.initials: J
authors.lastname: Copps
authors.forename: Shawn
authors.initials: S
authors.lastname: Ahmed
authors.forename: Richard F
authors.initials: RF
authors.lastname: Murphy
authors.forename: Sándor
authors.initials: S
authors.lastname: Lovas
mesh_terms: D002273:Carcinogens / Q000494:pharmacology*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D003110:Colonic Neoplasms / Q000209:etiology / Q000378:metabolism* / Q000473:pathology*; D005755:Gastrins / Q000494:pharmacology*; D006801:Humans; D010446:Peptide Fragments / Q000494:pharmacology; D011869:Radioligand Assay; D011949:Receptors, Cholecystokinin / Q000378:metabolism
chemical_list: D002273:Carcinogens; D005755:Gastrins; D010446:Peptide Fragments; D011949:Receptors, Cholecystokinin; C039260:gastrin hexapeptide; C013550:gastrin 17