Pathophysiology of Gastric NETs: Role of Gastrin and Menin

Abstract

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 p27^kip to the cytoplasm and its subsequent degradation by the proteasome.

Summary

Therapies that block degradation of p27^kip, the CCKBR2 gastrin receptor, or gastrin peptide are likely to facilitate treatment.

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