Pathophysiology of Gastric NETs: Role of Gastrin and Menin

Sinju Sundaresan, Anthony J. Kang, Juanita L. Merchant

Research output: Contribution to journalReview articlepeer-review

14 Scopus citations


Purpose of review: Neuroendocrine tumors (NETs) were initially identified as a separate entity in the early 1900s as a unique malignancy that secretes bioactive amines. GI-NETs are the most frequent type and represent a unique subset of NETs, because at least 75% of these tumors represent gastrin stimulation of the enterochromaffin-like cell located in the body of the stomach. The purpose of this review is to understand the specific role of gastrin in the generation of Gastric NETs (G-NETs). Recent findings: We review here the origin of enterochromaffin cells gut and the role of hypergastrinemia in gastric enteroendocrine tumorigenesis. We describe generation of the first genetically engineered mouse model of gastrin-driven G-NETs that mimics the human phenotype. The common mechanism observed in both the hypergastrinemic mouse model and human carcinoids is translocation of the cyclin-dependent inhibitor p27kip to the cytoplasm and its subsequent degradation by the proteasome. Summary: Therapies that block degradation of p27kip, the CCKBR2 gastrin receptor, or gastrin peptide are likely to facilitate treatment.

Original languageEnglish (US)
Article number32
JournalCurrent gastroenterology reports
Issue number7
StatePublished - Jul 1 2017
Externally publishedYes


  • ECL cells
  • MEN1
  • Proton pump inhibitors
  • Somatostatin
  • p27

ASJC Scopus subject areas

  • Gastroenterology


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