胃神经内分泌肿瘤的病理生理学：胃泌素和Menin的作用。
Pathophysiology of Gastric NETs: Role of Gastrin and Menin.
作者信息
Sundaresan Sinju, Kang Anthony J, Merchant Juanita L
机构信息
Division of Gastroenterology, Department of Internal Medicine, University of Michigan, BSRB, 2051, 109 Zina Pitcher PL, Ann Arbor, MI, 48109-2200, USA.
Department of Molecular and Integrative Physiology, University of Michigan, Ann Arbor, MI, USA.
出版信息
Curr Gastroenterol Rep. 2017 Jul;19(7):32. doi: 10.1007/s11894-017-0572-y.
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 to the cytoplasm and its subsequent degradation by the proteasome. Therapies that block degradation of p27, the CCKBR2 gastrin receptor, or gastrin peptide are likely to facilitate treatment.
综述目的
神经内分泌肿瘤（NETs）最初在20世纪初被确认为一种独立的实体，是一种分泌生物活性胺的独特恶性肿瘤。胃肠道神经内分泌肿瘤（GI-NETs）是最常见的类型，代表神经内分泌肿瘤的一个独特子集，因为这些肿瘤中至少75%表现为胃泌素对位于胃体部的肠嗜铬样细胞的刺激。本综述的目的是了解胃泌素在胃神经内分泌肿瘤（G-NETs）发生中的具体作用。
最新发现
我们在此回顾肠嗜铬细胞的起源以及高胃泌素血症在胃肠内分泌肿瘤发生中的作用。我们描述了首个模拟人类表型的胃泌素驱动的G-NETs基因工程小鼠模型的构建。在高胃泌素血症小鼠模型和人类类癌中观察到的共同机制是细胞周期蛋白依赖性抑制剂p27易位至细胞质并随后被蛋白酶体降解。阻断p27、胃泌素CCKBR2受体或胃泌素肽降解的疗法可能有助于治疗。
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