Dockray Graham, Dimaline Rod, Varro Andrea
Physiological Laboratory, University of Liverpool, Liverpool, UK.
Pflugers Arch. 2005 Jan;449(4):344-55. doi: 10.1007/s00424-004-1347-5. Epub 2004 Oct 5.
It is exactly a century since the gastric hormone gastrin was first described as a blood-borne regulator of gastric acid secretion. The identities of the main active forms of the hormone (the "classical gastrins") and their cellular and molecular sites of action in regulating acid secretion have all attracted sustained attention. However, recent work on peptides derived from the gastrin precursor that do not stimulate acid secretion ("non-classical gastrins"), together with studies on mice over-expressing the gene, or in which the gastrin gene has been deleted, suggest hitherto unsuspected roles in regulating cell proliferation, migration, and differentiation. Moreover, microarray and proteomic studies have identified previously unsuspected target genes of the classical gastrins. Some of the newer actions have implications for our understanding of the progression to cancer in oesophagus, stomach, pancreas and colon, all of which have recently been linked in one way or another to dysfunctional signalling involving products of the gastrin gene. The present review focuses on recent progress in understanding the biology of both classical and non-classical gastrins.
自胃激素胃泌素首次被描述为胃酸分泌的一种血源性调节因子以来，恰好已经过去了一个世纪。该激素的主要活性形式（“经典胃泌素”）的身份及其在调节胃酸分泌中的细胞和分子作用位点一直备受关注。然而，最近对源自胃泌素前体但不刺激胃酸分泌的肽（“非经典胃泌素”）的研究，以及对过表达该基因或胃泌素基因已被删除的小鼠的研究表明，它们在调节细胞增殖、迁移和分化方面具有迄今未被怀疑的作用。此外，微阵列和蛋白质组学研究已经确定了经典胃泌素以前未被怀疑的靶基因。其中一些新作用对我们理解食管癌、胃癌、胰腺癌和结肠癌的癌症进展具有重要意义，所有这些癌症最近都以某种方式与涉及胃泌素基因产物的功能失调信号传导相关联。本综述重点关注在理解经典和非经典胃泌素生物学方面的最新进展。
