Pathophysiology of Gastric NETs: Role of Gastrin and Menin

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

doi:10.1007/s11894-017-0572-y

Pathophysiology of Gastric NETs: Role of Gastrin and Menin

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

Research output: Contribution to journal › Review article › peer-review

14 Scopus citations

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.

Original language	English (US)
Article number	32
Journal	Current gastroenterology reports
Volume	19
Issue number	7
DOIs	https://doi.org/10.1007/s11894-017-0572-y
State	Published - Jul 1 2017
Externally published	Yes

Keywords

ECL cells
MEN1
Proton pump inhibitors
Somatostatin
p27

ASJC Scopus subject areas

Gastroenterology

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10.1007/s11894-017-0572-y

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title = "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 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.",

keywords = "ECL cells, MEN1, Proton pump inhibitors, Somatostatin, p27",

author = "Sinju Sundaresan and Kang, {Anthony J.} and Merchant, {Juanita L.}",

note = "Publisher Copyright: {\textcopyright} 2017, Springer Science+Business Media New York.",

year = "2017",

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doi = "10.1007/s11894-017-0572-y",

language = "English (US)",

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T2 - Role of Gastrin and Menin

AU - Sundaresan, Sinju

AU - Kang, Anthony J.

AU - Merchant, Juanita L.

PY - 2017/7/1

Y1 - 2017/7/1

N2 - 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.

AB - 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.

KW - ECL cells

KW - MEN1

KW - Proton pump inhibitors

KW - Somatostatin

KW - p27

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Pathophysiology of Gastric NETs: Role of Gastrin and Menin

Abstract

Keywords

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