Atlas of Genetics and Cytogenetics in Oncology and Haematology


Home   Genes   Leukemias   Solid Tumors   Cancer-Prone   Deep Insight   Case Reports   Journals  Portal   Teaching   

X Y 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 NA

GAST (gastrin)

Written2011-04Celia Chao, Mark R Hellmich
Department of Surgery, Sealy Center for Cancer Cell Biology, University of Texas Medical Branch, Galveston, TX 77555, USA

(Note : for Links provided by Atlas : click)

Identity

Alias_namesGAS
Other alias
HGNC (Hugo) GAST
LocusID (NCBI) 2520
Atlas_Id 44214
Location 17q21.2  [Link to chromosome band 17q21]
Location_base_pair Starts at 41712326 and ends at 41715969 bp from pter ( according to hg19-Feb_2009)  [Mapping GAST.png]
 
  Chromosome 17 - NC_000017.10.
Fusion genes
(updated 2017)
Data from Atlas, Mitelman, Cosmic Fusion, Fusion Cancer, TCGA fusion databases with official HUGO symbols (see references in chromosomal bands)
HAP1 (17q21.2) / GAST (17q21.2)

DNA/RNA

Note The 4.3 kb gene for human gastrin contains two introns and 3 exons that encode preprogastrin, the gastrin precursor. It is located on chromosome 17(q21), and consists of three exons that contain the code sequence for a prepropeptide of 101 amino acid residues with a calculated molecular mass of 11.4 kDa (see diagram below). The primary structure of human preprogastrin protein consists of an N-terminal 21-amino acid signal sequence followed by a spacer peptide, a bioactive domain, and finally a hexapeptide C-terminal flanking peptide (CTFP). Upon initiation of translation, the signal sequence facilitates the translocation of the elongating polypeptide into the endoplasmic reticulum (ER), where it is subsequently removed by a membrane-bound signal peptidase that cleaves the growing polypeptide chain between alanine residue 21 and serine 22 to generate the 80 amino acid peptide, progastrin. Progastrin is further processed (see protein section below) into the two principal C-terminal alpha-amidated forms of circulating gastrin generated from the proteolytic cleavage of progastrin are gastrin-17 (G17) and gastrin-34 (G34).
 
  Schematic representation of the preprogastrin gene, its mRNA, and the peptide precursor preprogastrin. The gene is transcribed as a 303 nucleotide RNA transcript and the mRNA is processed into a 101 amino acid (aa) preprohormone. The preprogastrin peptide consists of a 21-aa signal sequence, which is co-translationally cleaved, a N-terminal spacer, the active peptide and the C-terminal flanking peptide (CTFP). Progastrin is formed after removal of the signal peptide.

Protein

Note It should be noted that the numbering system of critical amino acid residues involved in peptide cleavage and post-translational modifications of gastrin varies within the scientific literature. This is due to the fact that the numbering system of some authors is based on the sequence of preprogastrin, which includes the 21 amino acids of the signal peptide sequence, whereas the numbering system of others is based on the sequence of progastrin. Our description of prohormone processing will be based on the 80 amino acid peptide sequence of progastrin.
After signal peptide cleavage, progastrin undergoes additional post-translational modifications as it transits from the ER through the Golgi to the trans-Golgi network before it is sorted into immature secretory vesicles of the regulated exocytosis (secretory) pathway. The modifications include O-sulfation at tyrosine residue 66 of the propeptide by tyrosylprotein sulfotransferases and/or phosphorylation at serine 75 by a calcium-dependent casein-like kinase. Although O-sulfation is thought to occur primarily in the trans-Golgi network, a recent study provides evidence suggesting that it may continue through later compartments of the regulated secretory pathway.
The extent of gastrin O-sulfation varies with species and cellular localization of peptide synthesis within the GI tract as well as the developmental stage of the tissues. For example, in adult humans, approximately half of the gastrin peptide synthesized in G cells of the antrum and duodenum, and released into the circulation are sulfated, whereas all of the gastrin peptide produced by the fetal pancreas appears to be sulfated. Functionally, sulfation of gastrin enhances endoproteolytic processing of progastrin, and may promote protein-protein interactions and peptide sorting between secretory pathways. However, unlike sulfation of the related peptide, cholecystokinin (CCK), sulfation of gastrin does not significantly affect its affinity for its physiologic receptor.
Phosphorylation of serine 75 of progastrin may promote proteolytic processing at the upstream arginine residues at positions 73 and 74 (arginine 73-arginine 74) releasing the C-terminal flanking peptide, and may affect the conversion of glycine-extended gastrin intermediates to mature C-terminal alpha-amidated peptides. However, since phosphorylation is not essential for progastrin processing, its biological significance remains an enigma.
Following sulfation and/or phosphorylation, progastrin exits the trans-Golgi network and enters immature granules of the regulated secretory pathway. The major proteolytic processing of progastrin to its biologically active peptides occurs in the maturing dense core secretory granules of the regulated pathway. Progastrin is cleaved by two types of proteases: endo- and exopeptidases. Endopeptidases, also known as prohormone convertases (PC), typically cleave polypeptides downstream of two adjacent basic amino acid residues at the general motif (lysine/arginine)-(X)n-(lysine/arginine), where n=0, 2, 4, or 6 and X is any amino acid, but usually not a Cysteine. PC1/3 and PC2 are involved in progastrin processing.
The two principal biologically active forms of circulating gastrin are gastrin-17 (G17) and gastrin-34 (G34). In rodent and human G cells of antrum and proximal duodenum, approximately 95% of the progastrin is processed to partially sulfated G17 (85%) and G34 (10%). Although G17 is the predominant product, G34 is the major circulating form of gastrin due to its slower rate of clearance. In both humans, the half-life of circulating G34 is approximately five times longer than that of G17.
The proteolytic processing of progastrin involves convertase-specific cleavage at three dibasic consensus sites. PC1/3 is active early in the secretory pathway in granules with a neutral pH (i.e., pH ≈ 7) and cleaves the prohormone after the arginine 36-arginine 37 and arginine 73-arginine 74 sequences, releasing the C-terminal flanking peptide, and generating G34. The post-cleavage residual basic residues are then removed by carboxypeptidase E, generating what are commonly referred to as the glycine-extended gastrins (i.e., G34-Glycine). In contrast to PC1/3, PC2 is mainly active in mature granules at an acidic pH (i.e., pH ≈ 5). Cleavage of G34-glycine by PC2 after the dibasic amino acid sequence lysine 53-lysine 54 produces G17-glycine. These glycine-extended peptides are substrates for the peptidyl-glycine alpha-amidating monooxygenase (PAM) that utilizes the glycyl residue as an amide donor to alpha-amidate the carboxyl group of the C-terminus of the peptide. The ratio of amidated gastrins to processing intermediates varies considerably across tissues and cell types. Processing intermediates are quite scarce in the gastric antrum, making up only about 1-5% of gastrin gene products, while in the duodenum the value has been reported to be as high as 20%. Carboxyl-terminus alpha-amidation is a prerequisite for high affinity binding of gastrin to its cognate receptor, CCK2 receptor.
 
  Processing of gastrin. The numbering system of critical amino acid residues involved in peptide cleavage and post-translational modifications of gastrin varies within the scientific literature. This is due to the fact that the numbering system of some authors is based on the sequence of preprogastrin, which includes the 21 amino acids of the signal peptide sequence, whereas the numbering system of others is based on the sequence of progastrin. The numbers at the top of the diagram represents the amino acid (aa) sequence for preprogastrin; the numbers at the bottom of the diagram represents the aa sequence for progastrin. The signal peptide is cleaved co-translationally in the rough ER by signal peptidase. In the Trans-Golgi-Network (TGN), progastrin is modified by sulfation at Tyr 66 and phosphorylation of Ser 75 by a casein-like kinase. Prohormone convertases (PC) and carboxypeptidase E (CPE) sequentially convert the prohormone to the glycine-extended forms (G71-Gly, G34-Gly, G17-Gly). Abbreviations: CTFP: C-terminal flanking peptide, TPST: tyrosyl-protein sulfotransferase, PAM: peptidyl-alpha-amidating-monooxygenase.

Mutations

Note There are no known mutations in the gastrin gene causing a pathologic entity. Overexpression of gastrin, or aberrant expression of gastrin, have both been associated with gastric, colorectal, esophageal and pancreatic cancers.

Implicated in

Note
  
Entity Gastrinomas
Note Gastrinomas are neuroendocrine tumors that can arise from the stomach, duodenum or pancreas. Patients with multiple endocrine neoplasia type 1 (MEN1) have a mutation in the menin gene and are at very high risk for developing gastrinomas. In patients with hypergastrinemia due to pernicious anemia or MEN1, tissue and plasma levels of PAI-2 are elevated. Gastrin directly regulates PAI-2 expression in CCK2 receptor-positive cells, and in neighboring receptor-negative cells, by way of paracrine mediators released from the CCK2 receptor-expressing cells. Direct regulation involves cell automous activation of CRE and AP-1 transcription factors via a PKC, Ras, Raf, RhoA, and the NFkappaB signaling pathways in CCK2 receptor-expressing cells by gastrin. The CRE and AP-1 transcription factors, in turn, regulate expression of the genes for IL-8 and COX2. IL-8 acts through a GACAGA site via the activating signal cointegrator 1 (ASC-1) complex, whereas prostaglandins, resulting from the activation of COX2, target the Myc-associated zinc finger protein (MAZ site via the small GTPase RhoA to stimulate PAI-2 expression in adjacent CCK2 receptor-negative cells.
  
  
Entity Inflammation-associated carcinomas
Note In a rat intestinal epithelial cell model, MAPKs mediate CCK2 receptor regulation of cyclooxgenase 2 (COX-2). COX-2 is an inducible enzyme catalyzing the rate-limiting step in prostaglandin synthesis, converting arachidonic acid to prostaglandin H2. A large body of genetic and biochemical evidence support the important role of COX-2 and the subsequent synthesis of prostaglandins in the regulation of inflammation and promotion of tumorigenesis. Gastrin has been shown to increase COX-2 expression in colorectal, gastric, and esophageal cancers.
  
  
Entity Gastric cancer
Note Gastric carcinogenesis is a multistep process that arises from superficial gastritis, chronic atrophic gastritis, progressing to intestinal metaplasia, dysplasia, and finally carcinoma. H. pylori is the most common known cause of chronic gastritis in humans, secretes urease, which converts urea to ammonia, and neutralizes the acid in the stomach. H. pylori initiates a host inflammatory response that is associated with the recruitment of mononuclear and polymorphonuclear leukocytes, and bone marrow-derived cells. Specific inflammatory cytokines from immune cells are required for the initiation and promotion of carcinogenesis. In addition to local inflammation, H. pylori induces the systemic elevation of serum gastrin (hypergastrinemia). The combination of achlorhydria and hypergastrinemia, induced by H. pylori infection, results in gastric bacterial overgrowth, lack of parietal cell differentiation, development of gastric metaplasia, and eventual progression to gastric carcinoma.
  
  
Entity Colorectal cancer
Note Gastrin and gastrin-like peptides are upregulated locally in 78% of premalignant adenomatous polyps, before the appearance of invasive carcinoma, and gastrin expression has been linked to key mutations in the initiation of colorectal carcinogenesis. When the APCmin-/+ mouse was crossed with a gastrin gene knockout mouse, the hybrid developed fewer intestinal polyps. Gastrin transcription is linked to the Wnt/beta-catenin pathway by a binding site for the transcription factor TCF4 in the gastrin promoter. Induction of the wild-type APC decreased gastrin mRNA expression, while transfection of constitutively active beta-catenin increased gastrin promoter activity.
  

Bibliography

Gastrin-induced cyclooxygenase-2 expression in Barrett's carcinogenesis.
Abdalla SI, Lao-Sirieix P, Novelli MR, Lovat LB, Sanderson IR, Fitzgerald RC.
Clin Cancer Res. 2004 Jul 15;10(14):4784-92.
PMID 15269153
 
Gastrin activates paracrine networks leading to induction of PAI-2 via MAZ and ASC-1.
Almeida-Vega S, Catlow K, Kenny S, Dimaline R, Varro A.
Am J Physiol Gastrointest Liver Physiol. 2009 Feb;296(2):G414-23. Epub 2008 Dec 12.
PMID 19074642
 
Gastrin induces leukocyte-endothelial cell interactions in vivo and contributes to the inflammation caused by Helicobacter pylori.
Alvarez A, Ibiza S, Hernandez C, Alvarez-Barrientos A, Esplugues JV, Calatayud S.
FASEB J. 2006 Nov;20(13):2396-8. Epub 2006 Oct 2.
PMID 17015411
 
Gastrins, cholecystokinins and gastrointestinal cancer.
Aly A, Shulkes A, Baldwin GS.
Biochim Biophys Acta. 2004 Jul 6;1704(1):1-10. (REVIEW)
PMID 15238241
 
Measurement and occurrence of sulfated gastrins.
Andersen BN.
Scand J Clin Lab Invest Suppl. 1984;168:5-24. (REVIEW)
PMID 6387882
 
Identification of a cis-regulatory element mediating somatostatin inhibition of epidermal growth factor-stimulated gastrin gene transcription.
Bachwich D, Merchant J, Brand SJ.
Mol Endocrinol. 1992 Aug;6(8):1175-84.
PMID 1357547
 
Evolution of gastrointestinal hormones: the cholecystokinin/gastrin family.
Baldwin GS, Patel O, Shulkes A.
Curr Opin Endocrinol Diabetes Obes. 2010 Feb;17(1):77-88. (REVIEW)
PMID 19952740
 
Control of preprogastrin messenger RNA translation by gastric acid in the rat.
Bate GW, Varro A, Dimaline R, Dockray GJ.
Gastroenterology. 1996 Nov;111(5):1224-9.
PMID 8898636
 
Gastrin mediated cholecystokinin-2 receptor activation induces loss of cell adhesion and scattering in epithelial MDCK cells.
Bierkamp C, Kowalski-Chauvel A, Dehez S, Fourmy D, Pradayrol L, Seva C.
Oncogene. 2002 Oct 31;21(50):7656-70.
PMID 12400008
 
Modulation of the cleavage of the gastrin precursor by prohormone phosphorylation.
Bishop L, Dimaline R, Blackmore C, Deavall D, Dockray GJ, Varro A.
Gastroenterology. 1998 Nov;115(5):1154-62.
PMID 9797370
 
Molecular cloning of human gastrin cDNA: evidence for evolution of gastrin by gene duplication.
Boel E, Vuust J, Norris F, Norris K, Wind A, Rehfeld JF, Marcker KA.
Proc Natl Acad Sci U S A. 1983 May;80(10):2866-9.
PMID 6574456
 
Complete tyrosine-O-sulphation of gastrin in neonatal rat pancreas.
Brand SJ, Andersen BN, Rehfeld JF.
Nature. 1984 May 31-Jun 6;309(5967):456-8.
PMID 6728000
 
Biosynthesis of tyrosine O-sulfated gastrins in rat antral mucosa.
Brand SJ, Klarlund J, Schwartz TW, Rehfeld JF.
J Biol Chem. 1984 Nov 10;259(21):13246-52.
PMID 6490654
 
Posttranslational processing of progastrin.
Bundgaard JR, Rehfeld JF.
Results Probl Cell Differ. 2010;50:207-20. (REVIEW)
PMID 19960379
 
Effect of cholecystokinin and gastrin on human peripheral blood lymphocyte functions, implication of cyclic AMP and interleukin 2.
Carrasco M, Hernanz A, De La Fuente M.
Regul Pept. 1997 Jun 18;70(2-3):135-42.
PMID 9272625
 
IL1B promoter polymorphism regulates the expression of gastric acid stimulating hormone gastrin.
Chakravorty M, Datta De D, Choudhury A, Roychoudhury S.
Int J Biochem Cell Biol. 2009 Jul;41(7):1502-10. Epub 2009 Jan 8.
PMID 19166966
 
Acute responses of rat stomach enterochromaffinlike cells to gastrin: secretory activation and adaptation.
Chen D, Monstein HJ, Nylander AG, Zhao CM, Sundler F, Hakanson R.
Gastroenterology. 1994 Jul;107(1):18-27.
PMID 7517373
 
Glycine-extended gastrin synergizes with gastrin 17 to stimulate acid secretion in gastrin-deficient mice.
Chen D, Zhao CM, Dockray GJ, Varro A, Van Hoek A, Sinclair NF, Wang TC, Koh TJ.
Gastroenterology. 2000 Sep;119(3):756-65.
PMID 10982770
 
Gastrin induction of histamine release from primary cultures of canine oxyntic mucosal cells.
Chuang CN, Tanner M, Chen MC, Davidson S, Soll AH.
Am J Physiol. 1992 Oct;263(4 Pt 1):G460-5.
PMID 1384357
 
EGF stimulates gastrin promoter through activation of Sp1 kinase activity.
Chupreta S, Du M, Todisco A, Merchant JL.
Am J Physiol Cell Physiol. 2000 Apr;278(4):C697-708.
PMID 10751319
 
Gastrin promotes human colon cancer cell growth via CCK-2 receptor-mediated cyclooxygenase-2 induction and prostaglandin E2 production.
Colucci R, Blandizzi C, Tanini M, Vassalle C, Breschi MC, Del Tacca M.
Br J Pharmacol. 2005 Feb;144(3):338-48.
PMID 15655524
 
Modulation of human neutrophil function in vitro by gastrin.
De la Fuente M, Carrasco M, Hernanz A.
J Endocrinol. 1997 Jun;153(3):475-83.
PMID 9204002
 
Specificity of prohormone convertase endoproteolysis of progastrin in AtT-20 cells.
Dickinson CJ, Sawada M, Guo YJ, Finniss S, Yamada T.
J Clin Invest. 1995 Sep;96(3):1425-31.
PMID 7657815
 
Food stimulation of histidine decarboxylase messenger RNA abundance in rat gastric fundus.
Dimaline R, Sandvik AK, Evans D, Forster ER, Dockray GJ.
J Physiol. 1993 Jun;465:449-58.
PMID 8229845
 
The gastrins: their production and biological activities.
Dockray GJ, Varro A, Dimaline R, Wang T.
Annu Rev Physiol. 2001;63:119-39. (REVIEW)
PMID 11181951
 
The calcium-sensing receptor acts as a modulator of gastric acid secretion in freshly isolated human gastric glands.
Dufner MM, Kirchhoff P, Remy C, Hafner P, Muller MK, Cheng SX, Tang LQ, Hebert SC, Geibel JP, Wagner CA.
Am J Physiol Gastrointest Liver Physiol. 2005 Dec;289(6):G1084-90. Epub 2005 Aug 18.
PMID 16109841
 
Gastrin response to candidate messengers in intact conscious rats monitored by antrum microdialysis.
Ericsson P, Hakanson R, Norlen P.
Regul Pept. 2010 Aug 9;163(1-3):24-30. Epub 2010 Mar 25.
PMID 20346991
 
Role of gastrin heptadecapeptide in the acid secretory response to amino acids in man.
Feldman M, Walsh JH, Wong HC, Richardson CT.
J Clin Invest. 1978 Feb;61(2):308-13.
PMID 621275
 
Calcium-sensing receptor is a physiologic multimodal chemosensor regulating gastric G-cell growth and gastrin secretion.
Feng J, Petersen CD, Coy DH, Jiang JK, Thomas CJ, Pollak Mr, Wa~k SA.
Proc Natl Acad Sci U S A. 2010 Oct 12;107(41):17791-6. Epub 2010 Sep 27.
PMID 20876097
 
Involvement of JAK2 upstream of the PI 3-kinase in cell-cell adhesion regulation by gastrin.
Ferrand A, Kowalski-Chauvel A, Bertrand C, Pradayrol L, Fourmy D, Dufresne M, Seva C.
Exp Cell Res. 2004 Dec 10;301(2):128-38.
PMID 15530849
 
EGF receptor activation stimulates endogenous gastrin gene expression in canine G cells and human gastric cell cultures.
Ford MG, Valle JD, Soroka CJ, Merchant JL.
J Clin Invest. 1997 Jun 1;99(11):2762-71.
PMID 9169507
 
Impaired gastric acid secretion in gastrin-deficient mice.
Friis-Hansen L, Sundler F, Li Y, Gillespie PJ, Saunders TL, Greenson JK, Owyang C, Rehfeld JF, Samuelson LC.
Am J Physiol. 1998 Mar;274(3 Pt 1):G561-8.
PMID 9530158
 
The Constitution and Properties of Two Gastrins Extracted from Hog Antral Mucosa.
Gregory RA, Tracy HJ.
Gut. 1964 Apr;5:103-14.
PMID 14159395
 
Gastrin stimulates cyclooxygenase-2 expression in intestinal epithelial cells through multiple signaling pathways. Evidence for involvement of ERK5 kinase and transactivation of the epidermal growth factor receptor.
Guo YS, Cheng JZ, Jin GF, Gutkind JS, Hellmich MR, Townsend CM Jr.
J Biol Chem. 2002 Dec 13;277(50):48755-63. Epub 2002 Sep 17.
PMID 12239223
 
Gastrin induces proliferation in Barrett's metaplasia through activation of the CCK2 receptor.
Haigh CR, Attwood SE, Thompson DG, Jankowski JA, Kirton CM, Pritchard DM, Varro A, Dimaline R.
Gastroenterology. 2003 Mar;124(3):615-25.
PMID 12612900
 
An antiapoptotic role for gastrin and the gastrin/CCK-2 receptor in Barrett's esophagus.
Harris JC, Clarke PA, Awan A, Jankowski J, Watson SA.
Cancer Res. 2004 Mar 15;64(6):1915-9.
PMID 15026323
 
Molecular basis of colorectal cancer - role of gastrin and cyclooxygenase-2.
Hartwich J, Konturek SJ, Pierzchalski P, Zuchowicz M, Konturek PC, Bielanski W, Marlicz K, Starzynska T, Lawniczak M.
Med Sci Monit. 2001 Nov-Dec;7(6):1171-81.
PMID 11687726
 
Gastric acid secretion.
Hersey SJ, Sachs G.
Physiol Rev. 1995 Jan;75(1):155-89. (REVIEW)
PMID 7831396
 
Effects of fundic vagotomy and cholinergic replacement on pentagastrin dose responsive gastric acid and pepsin secretion in man.
Hirschowitz BI, Helman CA.
Gut. 1982 Aug;23(8):675-82.
PMID 6807759
 
Hypergastrinemia develops within 24 hours of truncal vagotomy in dogs.
Hollinshead JW, Debas HT, Yamada T, Elashoff J, Osadchey B, Walsh JH.
Gastroenterology. 1985 Jan;88(1 Pt 1):35-40.
PMID 2856878
 
GRP nerves in pig antrum: role of GRP in vagal control of gastrin secretion.
Holst JJ, Knuhtsen S, Orskov C, Skak-Nielsen T, Poulsen SS, Jensen SL, Nielsen OV.
Am J Physiol. 1987 Nov;253(5 Pt 1):G643-9.
PMID 2446506
 
Gastrin induces the interaction between human mononuclear leukocytes and endothelial cells through the endothelial expression of P-selectin and VCAM-1.
Ibiza S, Alvarez A, Romero W, Barrachina MD, Esplugues JV, Calatayud S.
Am J Physiol Cell Physiol. 2009 Dec;297(6):C1588-95. Epub 2009 Oct 7.
PMID 19812370
 
Structural analysis of the gene encoding human gastrin: the large intron contains an Alu sequence.
Ito R, Sato K, Helmer T, Jay G, Agarwal K.
Proc Natl Acad Sci U S A. 1984 Aug;81(15):4662-6.
PMID 6087340
 
Consequences of long-term proton pump blockade: insights from studies of patients with gastrinomas.
Jensen RT.
Basic Clin Pharmacol Toxicol. 2006 Jan;98(1):4-19. (REVIEW)
PMID 16433886
 
Progastrin processing during antral G-cell hypersecretion in humans.
Jensen S, Borch K, Hilsted L, Rehfeld JF.
Gastroenterology. 1989 Apr;96(4):1063-70.
PMID 2925053
 
Inactivating cholecystokinin-2 receptor inhibits progastrin-dependent colonic crypt fission, proliferation, and colorectal cancer in mice.
Jin G, Ramanathan V, Quante M, Baik GH, Yang X, Wang SS, Tu S, Gordon SA, Pritchard DM, Varro A, Shulkes A, Wang TC.
J Clin Invest. 2009 Sep;119(9):2691-701. doi: 10.1172/JCI38918. Epub 2009 Aug 3.
PMID 19652364
 
Inhibition of gastrin gene expression by somatostatin.
Karnik PS, Monahan SJ, Wolfe MM.
J Clin Invest. 1989 Feb;83(2):367-72.
PMID 2563264
 
Somatostatin stimulates gastrin mRNA turnover in dog antral mucosa.
Karnik PS, Wolfe MM.
J Biol Chem. 1990 Feb 15;265(5):2550-5.
PMID 1968059
 
Delineation of the chemomechanosensory regulation of gastrin secretion using pure rodent G cells.
Kidd M, Hauso O, Drozdov I, Gustafsson BI, Modlin IM.
Gastroenterology. 2009 Jul;137(1):231-41, 241.e1-10. Epub 2009 Jan 14.
PMID 19208342
 
Regulation of parietal cell migration by gastrin in the mouse.
Kirton CM, Wang T, Dockray GJ.
Am J Physiol Gastrointest Liver Physiol. 2002 Sep;283(3):G787-93.
PMID 12181195
 
Gastrin is a target of the beta-catenin/TCF-4 growth-signaling pathway in a model of intestinal polyposis.
Koh TJ, Bulitta CJ, Fleming JV, Dockray GJ, Varro A, Wang TC.
J Clin Invest. 2000 Aug;106(4):533-9.
PMID 10953028
 
Gastrin deficiency results in altered gastric differentiation and decreased colonic proliferation in mice.
Koh TJ, Goldenring JR, Ito S, Mashimo H, Kopin AS, Varro A, Dockray GJ, Wang TC.
Gastroenterology. 1997 Sep;113(3):1015-25.
PMID 9287997
 
Helicobacter pylori, gastrin and cyclooxygenases in gastric cancer.
Konturek PC, Hartwich A, Zuchowicz M, Labza H, Pierzchalski P, Karczewska E, Bielanski W, Hahn EG, Konturek SJ.
J Physiol Pharmacol. 2000 Dec;51(4 Pt 1):737-49.
PMID 11192946
 
Studies on serum gastrin levels in pernicious anaemia.
Korman MG, John DJ, Hansky J.
Gut. 1970 Nov;11(11):981.
PMID 5492264
 
Gastrin is a major mediator of the gastric phase of acid secretion in dogs: proof by monoclonal antibody neutralization.
Kovacs TO, Walsh JH, Maxwell V, Wong HC, Azuma T, Katt E.
Gastroenterology. 1989 Dec;97(6):1406-13.
PMID 2583408
 
Disturbed progastrin processing in carboxypeptidase E-deficient fat mice.
Lacourse KA, Friis-Hansen L, Rehfeld JF, Samuelson LC.
FEBS Lett. 1997 Oct 13;416(1):45-50.
PMID 9369230
 
Plasma gastrin and gastric enterochromaffinlike cell activation and proliferation. Studies with omeprazole and ranitidine in intact and antrectomized rats.
Larsson H, Carlsson E, Mattsson H, Lundell L, Sundler F, Sundell G, Wallmark B, Watanabe T, Hakanson R.
Gastroenterology. 1986 Feb;90(2):391-9.
PMID 3510144
 
Pancreatic gastrin in foetal and neonatal rats.
Larsson LI, Rehfeld JF, Sundler F, Hakanson R.
Nature. 1976 Aug 12;262(5569):609-10.
PMID 958427
 
Mononuclear cells and cytokines stimulate gastrin release from canine antral cells in primary culture.
Lehmann FS, Golodner EH, Wang J, Chen MC, Avedian D, Calam J, Walsh JH, Dubinett S, Soll AH.
Am J Physiol. 1996 May;270(5 Pt 1):G783-8.
PMID 8967489
 
The murine gastrin promoter is synergistically activated by transforming growth factor-beta/Smad and Wnt signaling pathways.
Lei S, Dubeykovskiy A, Chakladar A, Wojtukiewicz L, Wang TC.
J Biol Chem. 2004 Oct 8;279(41):42492-502. Epub 2004 Jul 28.
PMID 15292219
 
The genes for human gastrin and cholecystokinin are located on different chromosomes.
Lund T, Geurts van Kessel AH, Haun S, Dixon JE.
Hum Genet. 1986 May;73(1):77-80.
PMID 3011648
 
Role of acetylcholine and gastrin-releasing peptide (GRP) in gastrin secretion.
Matsuno M, Matsui T, Iwasaki A, Arakawa Y.
J Gastroenterol. 1997 Oct;32(5):579-8>./TR>
PMID 9349981
 
Coexpression of gastrin and gastrin receptors (CCK-B and delta CCK-B) in gastrointestinal tumour cell lines.
McWilliams DF, Watson SA, Crosbee DM, Michaeli D, Seth R.
Gut. 1998 Jun;42(6):795-8.
PMID 9691917
 
Sp1 phosphorylation by Erk 2 stimulates DNA binding.
Merchant JL, Du M, Todisco A.
Biochem Biophys Res Commun. 1999 Jan 19;254(2):454-61.
PMID 9918860
 
Gastrin induces heparin-binding epidermal growth factor-like growth factor in rat gastric epithelial cells transfected with gastrin receptor.
Miyazaki Y, Shinomura Y, Tsutsui S, Zushi S, Higashimoto Y, Kanayama S, Higashiyama S, Taniguchi N, Matsuzawa Y.
Gastroenterologq. 19=9Jan;116(1):78-89.
PMID 9869605
 
Gastrin suppresses growth of CCK2 receptor expressing colon cancer cells by inducing apoptosis in vitro and in vivo.
Muerkoster S, Isberner A, Arlt A, Witt M, Reimann B, Blaszczuk E, Werbing V, Folsch UR, Schmitz F, Schafer H.
Gastroenterology. 2005 Sep;129(3):952-68.
PMID 16143134
 
Gastrin stimulates the growth of gastric pit cell precursors by inducing its own receptors.
Nakajima T, Konda Y, Izumi Y, Kanai M, Hayashi N, Chiba T, Takeuchi T.
Am J Physiol Gastrointest Liver Physiol. 2002 Feb;282(2):G359-66.
PMID 11804858
 
Oncogenic ras induces gastrin gene expression in colon cancer.
Nakata H, Wang SL, Chung DC, Westwick JK, Tillotson LG.
Gastroenterology. 1998 Nov;115(5):1144-53.
PMID 9797369
 
Vagal regulation of GRP, gastric somatostatin, and gastrin secretion in vitro.
Nishi S, Seino Y, Takemura J, Ishida H, Seno M, Chiba T, Yanaihara C, Yanaihara N, Imura H.
Am J Physiol. 1985 Apr;248(4 Pt 1):E425-31.
PMID 2858978
 
Gastrin mediates the gastric mucosal proliferative response to feeding.
Ohning GV, Wong HC, Lloyd KC, Walsh JH.
Am J Physiol. 1996 Sep;271(3 Pt 1):G470-6.
PMID 8843772
 
Agonist-independent activation of Src tyrosine kinase by a cholecystokinin-2 (CCK2) receptor splice variant.
Olszewska-Pazdrak B, Townsend CM Jr, Hellmich MR.
J Biol Chem. 2004 Sep 24;279(39):40400-4. Epub 2004 Jul 29.
PMID 15292208
 
Gastrin increases murine intestinal crypt regeneration following injury.
Ottewell PD, Duckworth CA, Varro A, Dimaline R, Wang TC, Watson AJ, Dockray GJ, Pritchard DM.
Gastroenterology. 2006 Apr;130(4):1169-80.
PMID 16618411
 
Gastrin effects on isolated rat enterochromaffin-like cells in primary culture.
Prinz C, Scott DR, Hurwitz D, Helander HF, Sachs G.
Am J Physiol. 1994 Oct;267(4 Pt 1):G663-75.
PMID 7524350
 
Prohormone convertases 1/3 and 2 together orchestrate the site-specific cleavages of progastrin to release gastrin-34 and gastrin-17.
Rehfeld JF, Zhu X, Norrbom C, Bundgaard JR, Johnsen AH, Nielsen JE, Vikesaa J, Stein J, Dey A, Steiner DF, Friis-Hansen L.
Biochem J. 2008 Oct 1;415(1):35-43.
PMID 18554181
 
Stimulation of gastrin secretion in vitro by intraluminal chemicals: regulation by intramural cholinergic and noncholinergic neurons.
Saffouri B, DuVal JW, Makhlouf GM.
Gastroenterology. 1984 Sep;87(3):557-61.
PMID 6146551
 
Gastrin regulates histidine decarboxylase activity and mRNA abundance in rat oxyntic mucosa.
Sandvik AK, Dimaline R, Marvik R, Brenna E, Waldum HL.
Am J Physiol. 1994 Aug;267(2 Pt 1):G254-8.
PMID 8074225
 
Peptone stimulates gastrin secretion from the stomach by activating bombesin/GRP and cholinergic neurons.
Schubert ML, Coy DH, Makhlouf GM.
Am J Physiol. 1992 Apr;262(4 Pt 1):G685-9.
PMID 1348906
 
Biology and pathology of non-amidated gastrins.
Shulkes A, Baldwin G.
Scand J Clin Lab Invest Suppl. 2001;234:123-8. (REVIEW)
PMID 11713973
 
Gastrin regulates the heparin-binding epidermal-like growth factor promoter via a PKC/EGFR-dependent mechanism.
Sinclair NF, Ai W, Raychowdhury R, Bi M, Wang TC, Koh TJ, McLaughlin JT.
Am J Physiol Gastrointest Liver Physiol. 2004 Jun;286(6):G992-9. Epub 2004 Feb 5.
PMID 14764442
 
Gastrin and gastrin receptor activation: an early event in the adenoma-carcinoma sequence.
Smith AM, Watson SA.
Gut. 2000 Dec;47(6):820-4.
PMID 11076881
 
Release of gastrin by epinephrine in man.
Stadil F, Rehfeld JF.
Gastroenterology. 1973 Aug;65(2):210-5.
PMID 4720024
 
Effect of individual l-amino acids on gastric acid secretion and serum gastrin and pancreatic polypeptide release in humans.
Taylor IL, Byrne WJ, Christie DL, Ament ME, Walsh JH.
Gastroenterology. 1982 Jul;83(1 Pt 2):273-8.
PMID 6806140
 
Effect of selective proximal vagotomy and truncal vagotomy on gastric acid and serum gastrin responses to a meal in duodenal ulcer patients.
Thompson JC, Lowder WS, Peurifoy JT, Swierczek JS, Rayford PL.
Ann Surg. 1978 Oct;188(4):431-8.
PMID 697427
 
RIN ZF, a novel zinc finger gene, encodes proteins that bind to the CACC element of the gastrin promoter.
Tillotson LG.
J Biol Chem. 1999 Mar 19;274(12):8123-8.
PMID 10075714
 
Molecular mechanisms for the antiapoptotic action of gastrin.
Todisco A, Ramamoorthy S, Witham T, Pausawasdi N, Srinivasan S, Dickinson CJ, Askari FK, Krametter D.
Am J Physiol Gastrointest Liver Physiol. 2001 Feb;280(2):G298-307.
PMID 11208554
 
Molecular mechanisms for the growth factor action of gastrin.
Todisco A, Takeuchi Y, Urumov A, Yamada J, Stepan VM, Yamada T.
Am J Physiol. 1997 Oct;273(4 Pt 1):G891-8.
PMID 9357832
 
The human gastrin precursor. Characterization of phosphorylated forms and fragments.
Varro A, Desmond H, Pauwels S, Gregory H, Young J, Dockray GJ.
Biochem J. 1988 Dec 15;256(3):951-7.
PMID 3223964
 
Modulation of posttranslational processing of gastrin precursor in dogs.
Varro A, Nemeth J, Bridson J, Lonovics J, Dockray GJ.
Am J Physiol. 1990 Jun;258(6 Pt 1):G904-9.
PMID 2360636
 
The gastrin-histamine sequence.
Waldum HL, Sandvik AK, Brenna E, Kleveland PM.
Gastroenterology. 1996 Sep;111(3):838-9.
PMID 8780600
 
Pure human big gastrin. Immunochemical properties, disappearance half time, and acid-stimulating action in dogs.
Walsh JH, Debas HT, Grossman MI.
J Clin Invest. 1974 Aug;54(2):477-85.
PMID 4847254
 
Clearance and acid-stimulating action of human big and little gastrins in duodenal ulcer subjects.
Walsh JH, Isenberg JI, Ansfield J, Maxwell V.
J Clin Invest. 1976 May;57(5):1125-31.
PMID 1262460
 
Structure of a human gastrin gene.
Wiborg O, Berglund L, Boel E, Norris F, Norris K, Rehfeld JF, Marcker KA, Vuust J.
Proc Natl Acad Sci U S A. 1984 Feb;81(4):1067-9.
PMID 6322186
 
Gastrin-stimulated gastric epithelial cell invasion: the role and mechanism of increased matrix metalloproteinase 9 expression.
Wroblewski LE, Pritchard DM, Carter S, Varro A.
Biochem J. 2002 Aug 1;365(Pt 3):873-9.
PMID 11971760
 
Effects of inhibition of gastric secretion on antral gastrin and somatostatin gene expression in rats.
Wu SV, Giraud A, Mogard M, Sumii K, Walsh JH.
Am J Physiol. 1990 May;258(5 Pt 1):G788-93.
PMID 1692193
 
Studies of regulation of gastrin synthesis and post-translational processing by molecular biology approaches.
Wu SV, Sumii K, Walsh JH.
Ann N Y Acad Sci. 1990;597:17-27.
PMID 1974754
 

Citation

This paper should be referenced as such :
Chao, C ; Hellmich, MR
GAST (gastrin)
Atlas Genet Cytogenet Oncol Haematol. 2011;15(11):921-927.
Free journal version : [ pdf ]   [ DOI ]
On line version : http://AtlasGeneticsOncology.org/Genes/GASTID44214ch17q21.html


Other Solid tumors implicated (Data extracted from papers in the Atlas) [ 1 ]
  Neuro-Endocrine/Endocrine System: Carcinoid tumors


External links

Nomenclature
HGNC (Hugo)GAST   4164
Cards
AtlasGASTID44214ch17q21
Entrez_Gene (NCBI)GAST  2520  gastrin
AliasesGAS
GeneCards (Weizmann)GAST
Ensembl hg19 (Hinxton)ENSG00000184502 [Gene_View]
Ensembl hg38 (Hinxton)ENSG00000184502 [Gene_View]  chr17:41712326-41715969 [Contig_View]  GAST [Vega]
ICGC DataPortalENSG°0000q84702
TCGA cBioPortalGAST
AceView (NCBI)GAST
Genatlas (Paris)GAST
WikiGenes2520
SOURCE (Princeton)GAST
Genetics Home Reference (NIH)GAST
Genomic and cartography
GoldenPath hg38 (UCSC)GAST  -     chr17:41712326-41715969 +  17q21.2   [Description]    (hg38-Dec_2013)
GoldenPath hg19 (UCSC)GAST  -     17q21.2   [Description]    (hg19-Feb_2009)
EnsemblGAST - 17q21.2 [CytoView hg19]  GAST - 17q21.2 [CytoView hg38]
Mapping of homologs : NCBIGAST [Mapview hg19]  GAST [Mapview hg38]
OMIM137250   
Gene and transcription
Genbank (Entrez)BC069724 BC069762 BM768483 BM768762 HQ448465
RefSeq transcript (Entrez)NM_000805
RefSeq genomic (Entrez)
Consensus coding sequences : CCDS (NCBI)GAST
Cluster EST : UnigeneHs.2681 [ NCBI ]
CGAP (NCI)Hs.2681
Alternative Splicing GalleryENSG00000184502
Gene ExpressionGAST [ NCBI-GEO ]   GAST [ EBI - ARRAY_EXPRESS ]   GAST [ SEEK ]   GAST [ MEM ]
Gene Expression Viewer (FireBrowse)GAST [ Firebrowse - Broad ]
SOURCE (Princeton)Expression in : [Datasets]   [Normal Tissue Atlas]  [carcinoma Classsification]  [NCI60]
GenevestigatorExpression in : [tissues]  [cell-lines]  [cancer]  [perturbations]  
BioGPS (Tissue expression)2520
GTEX Portal (Tissue expression)GAST
Human Protein AtlasENSG00000184502-GAST [pathology]   [cell]   [tissue]
Protein : pattern, domain, 3D structure
UniProt/SwissProtP01350   [function]  [subcellular_location]  [family_and_domains]  [pathology_and_biotech]  [ptm_processing]  [expression]  [interaction]
NextProtP01350  [Sequence]  [Exons]  [Medical]  [Publications]
With graphics : InterProP01350
Splice isoforms : SwissVarP01350
PhosPhoSitePlusP01350
Domaine pattern : Prosite (Expaxy)GASTRIN (PS00259)   
Domains : Interpro (EBI)Gastrin    Gastrin/cholecystokinin_CS   
Domain f`milées$: Pfam (Sanger)Gastrin (PF00918)   
Domain families : Pfam (NCBI)pfam00918   
Conserved Domain (NCBI)GAST
DMDM Disease mutations2520
Blocks (Seattle)GAST
SuperfamilyP01350
Human Protein Atlas [tissue]ENSG00000184502-GAST [tissue]
Peptide AtlasP01350
HPRD
IPIIPI00001624   
Protein Interaction databases
DIP (DOE-UCLA)P01350
IntAct (EBI)P01350
FunCoupENSG00000184502
BioGRIDGAST
STRING (EMBL)GAST
ZODIACGAST
Ontologies - Pathways
QuickGOP01350
Ontology : AmiGOhormone activity  protein binding  extracellular region  extracellular space  signal transduction  G-protein coupled receptor signaling pathway  response to food  
Ontology : EGO-EBIhormone activity  protein binding  extracellular region  extracellular space  signal transduction  G-protein coupled receptor signaling pathway  response to food  
Pathways : KEGGGastric acid secretion   
REACTOMEP01350 [protein]
REACTOME PathwaysR-HSA-881907 [pathway]   
NDEx NetworkGAST
Atlas of Cancer Signalling NetworkGAST
Wikipedia pathwaysGAST
Orthology - Evolution
OrthoDB2520
GeneTree (enSembl)ENSG00000184502
Phylogenetic Trees/Animal Genes : TreeFamGAST
HOVERGENP01350
HOGENOMP01350
Homologs : HomoloGeneGAST
Homology/Alignments : Family Browser (UCSC)GAST
Gene fusions - Rearrangements
Fusion : MitelmanHAP1/GAST [17q21.2/17q21.2]  [t(17;17)(q21;q21)]  
Fusion: TCGA_MDACCHAP1 17q21.2 GAST 17q21.2 BRCA
Tumor Fusion PortalGAST
Polymorphisms : SNP and Copy number variants
NCBI Variation ViewerGAST [hg38]
dbSNP Single Nucleotide Polymorphism (NCBI)GAST
dbVarGAST
ClinVarGAST
1000_GenomesGAST 
Exome Variant ServerGAST
ExAC (Exome Aggregation Consortium)ENSG00000184502
GNOMAD BrowserENSG00000184502
Genetic variants : HAPMAP2520
Genomic Variants (DGV)GAST [DGVbeta]
DECIPHERGAST [patients]   [syndromes]   [variants]   [genes]  
CONAN: Copy Number AnalysisGAST 
Mutations
ICGC Data PortalGAST 
TCGA Data PortalGAST 
Broad Tumor PortalGAST
OASIS PortalGAST [ Somatic mutations - Copy number]
Somatic Mutations in Cancer : COSMICGAST  [overview]  [genome browser]  [tissue]  [distribution]  
Mutations and Diseases : HGMDGAST
LOVD (Leiden Open Variation Database)Whole genome datasets
LOVD (Leiden Open Variation Database)LOVD - Leiden Open Variation Database
LOVD (Leiden Open Variation Database)LOVD 3.0 shared installation
BioMutasearch GAST
DgiDB (Drug Gene Interaction Database)GAST
DoCM (Curated mutations)GAST (select the gene name)
CIViC (Clinical Interpretations of Variants in Cancer)GAST (select a term)
intoGenGAST
NCG5 (London)GAST
Cancer3DGAST(select the gene name)
Impact of mutations[PolyPhen2] [SIFT Human Coding SNP] [Buck Institute : MutDB] [Mutation Assessor] [Mutanalyser]
Diseases
OMIM137250   
Orphanet
DisGeNETGAST
MedgenGAST
Genetic Testing Registry GAST
NextProtP01350 [Medical]
TSGene2520
GENETestsGAST
Target ValidationGAST
Huge Navigator GAST [HugePedia]
snp3D : Map Gene to Disease2520
BioCentury BCIQGAST
ClinGenGAST
Clinical trials, drugs, therapy
Chemical/Protein Interactions : CTD2520
Chemical/Pharm GKB GenePA28577
Clinical trialGAST
Miscellaneous
canSAR (ICR)GAST (select the gene name)
Other databaseThe Pancreapedia
Probes
Litterature
PubMed102 Pubmed reference(s) in Entrez
GeneRIFsGene References Into Functions (Entrez)
CoreMineGAST
EVEXGAST
GoPubMedGAST
iHOPGAST
REVIEW articlesautomatic search in PubMed
Last year publicationsautomatic search in PubMed

Search in all EBI   NCBI

© Atlas of Genetics and Cytogenetics in Oncology and Haematology
indexed on : Tue Nov 21 14:51:18 CET 2017

Home   Genes   Leukemias   Solid Tumors   Cancer-Prone   Deep Insight   Case Reports   Journals  Portal   Teaching   

For comments and suggestions or contributions, please contact us

jlhuret@AtlasGeneticsOncology.org.