RGD Reference Report - Mutations of RegIalpha are associated with enterochromaffin-like cell tumor development in patients with hypergastrinemia. - Rat Genome Database

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Mutations of RegIalpha are associated with enterochromaffin-like cell tumor development in patients with hypergastrinemia.

Authors: Higham, AD  Bishop, LA  Dimaline, R  Blackmore, CG  Dobbins, AC  Varro, A  Thompson, DG  Dockray, GJ 
Citation: Higham AD, etal., Gastroenterology. 1999 Jun;116(6):1310-8.
RGD ID: 9850135
Pubmed: PMID:10348814   (View Abstract at PubMed)

BACKGROUND & AIMS: The RegIalpha gene (Reg) encodes a secretory protein proposed to regulate islet beta-cell and gastric mucous cell growth. Reg is expressed in rat gastric enterochromaffin-like (ECL) cells. The aim of this study was to examine Reg expression in human corpus and to determine the identity of Reg in ECL cell carcinoid tumors in hypergastrinemic patients. METHODS: Reg messenger RNA (mRNA) abundance was quantified by Northern blot in extracts of gastric corpus from patients with and without ECL cell tumors and in AR4-2J cells stimulated by gastrin; cellular origins were determined by immunocytochemistry. Mutations of Reg were determined by reverse-transcription polymerase chain reaction, cloning, and sequencing, and the mutated protein was expressed in HIT-T15 cells. RESULTS: Reg mRNA abundance was increased approximately threefold in the corpus of hypergastrinemic patients compared with controls, and was enriched in 3 of 7 ECL cell carcinoid tumors but not in non-endocrine cell gastric polyps. In AR4-2J cells, gastrin stimulated Reg mRNA abundance; this was eliminated by the gastrin/cholecystokinin B antagonist L-740,093 (10(-9) mol/L). Immunocytochemistry indicated that Reg was located in both chief cells and ECL cells in human corpus. Mutations of Reg were identified in 3 of 5 patients with ECL cell carcinoid tumors; in 2 cases, mutation of the initiator methionine residue led to exclusion of the protein from the secretory pathway. CONCLUSIONS: Gastrin regulates Reg mRNA abundance in human corpus. Mutations of Reg that prevent secretion are associated with ECL cell carcinoids, suggesting a function as an autocrine or paracrine tumor suppressor.



RGD Manual Disease Annotations    Click to see Annotation Detail View

  
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
REG1AHumanCarcinoid Tumor  IAGP associated with Hypergastrinemia and DNA:missense mutations:cds:multiple (human)RGD 
Reg1MouseCarcinoid Tumor  ISOREG1A (Homo sapiens)associated with Hypergastrinemia and DNA:missense mutations:cds:multiple (human)RGD 
Reg1aRatCarcinoid Tumor  ISOREG1A (Homo sapiens)associated with Hypergastrinemia and DNA:missense mutations:cds:multiple (human)RGD 
REG1AHumanHypergastrinemia  IEP mRNA:increased expression:gastric corpus (human)RGD 
Reg1MouseHypergastrinemia  ISOREG1A (Homo sapiens)mRNA:increased expression:gastric corpus (human)RGD 
Reg1aRatHypergastrinemia  ISOREG1A (Homo sapiens)mRNA:increased expression:gastric corpus (human)RGD 

Gene Ontology Annotations    Click to see Annotation Detail View

Biological Process

  
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
Reg1aRatcellular response to gastrin  IEP  RGD 

Objects Annotated

Genes (Rattus norvegicus)
Reg1a  (regenerating family member 1 alpha)

Genes (Mus musculus)
Reg1  (regenerating islet-derived 1)

Genes (Homo sapiens)
REG1A  (regenerating family member 1 alpha)


Additional Information