The Production and Role of Gastrin-17 and Gastrin-17-Gly in Gastrointestinal Cancers

Abstract

The gastrointestinal peptide hormone gastrin is responsible for initiating the release of gastric acid in the stomach in response to the presence of food and/or humoral factors such as gastrin releasing peptide. However, it has a role in the growth and maintenance of the gastric epithelium, and has been implicated in the formation and growth of gastric cancers. Hypergastrinemia resulting from atrophic gastritis and pernicious anemia leads to hyperplasia and carcinoid formation in rats, and contributes to tumor formation in humans. Additionally, gastrin has been suspected to play a role in the formation and growth of cancers of the colon, but recent studies have instead implicated gastrin processing intermediates, such as gastrin-17-Gly, acting upon a putative, non-cholecystokinin receptor. This review summarizes the production and chemical structures of gastrin and the processing intermediate gastrin-17-Gly, as well as their activities in the gastrointestinal tract, particularly the promotion of colon cancers. Gastrin processing in the GI tractJohn Sydney Edkins postulated in 1905 [1][2] that the acid secretory activity of the stomach could be attributed to the agent gastrin. The gastrin gene is expressed and gastrin secreted in a variety of cells in the body, among them those of the small and large intestine (duodenal, jejunal, ileal, and colonic mucosas), the pancreas, neuroendocrine tissue (the pituitary and hypothalamus, cerebellum, vagal nerve, and adrenal medulla), the genitals and the respiratory tract, where it serves a variety of purposes [3][4][5][6][7][8][9][10][11][12][13][14][15][16][17][18]. However, "mature" gastrin is predominantly manufactured by the antral mucosa of the stomach, where G endocrine cells secrete the peptide in response to the presence of amino acids, dietary amines, and calcium in the stomach, for the purpose of stimulating gastric acid secretion [19-25, reviewed in 26]. Neutralization of acid or inhibition of acid secretion also stimulates gastrin release [27][28][29][30][31][32][33]. In addition to luminal stimuli, basolateral stimuli of the G cells by GRP or Ach from nerve fibers, or by humoral factors such as EGF, also cause the expression and secretion of gastrin in some species [34][35]. In response to increased acid levels or VIP, D endocrine cells, in turn, secrete somatostatin, which acts to inhibit the secretion of gastrin.The expression of the gastrin gene and the processing of its polypeptide product in the gastrointestinal tract have been gradually revealed through extraction from gastrin-producing tissues and characterization of its processing intermediates with antibodies, chromatography and peptide analysis tools such as mass spectrometry. Genomic DNA information revealed the gastrin gene structure. The mRNA of the 101-residue gastrin precursor preprogastrin is translated at the endoplasmic reticulum, where an N-terminal signaling sequence is cleaved *Corresponding author: Sándor Lovas, Department of Biomedical Sciences, Creighton University School of Medi...

Enterohormonal disturbances in colorectal cancer patients

“…progastrin (precursor of gastrin) and glycine-extended gastrin [20], do not stimulate the acid secretion. These peptides can be found in all cells that express the gastrin gene, including colonic, lung, pancreatic, esophageal and gastric cancer cells [22,49,50]. Elevated blood levels of gastrin were shown to correlate positively with pancreatic cancer risk [51].…”

“…Autoimmune reactions, Helicobacter pylori infection and acid suppressing drugs may induce chronic atrophic gastritis and resultant hypochlorhydria, which eventually results in enhanced synthesis of gastrin. Presence of gastrin-secreting tumors, gastrinomas, predisposes to hypergastrinemia [23,36,50]. Elevated level of gastrin is currently recognized as a factor involved in pathogenesis of various gastric malignancies, among them gastric cancer [23,29,35].…”

“…Elevated level of gastrin is currently recognized as a factor involved in pathogenesis of various gastric malignancies, among them gastric cancer [23,29,35]. Endogenous hypergastrinemia was also shown to be associated with defects of rectal cell proliferation, and was implicated in development of colonic adenomas and adenocarcinomas [31,50,52,53]. Early stages of colorectal carcinogenesis are associated with activation of gastrin and gastrin/CCK-2 receptor genes within epithelial cells [32].…”

Diagnostic Values of Serum Levels of Pepsinogens and Gastrin-17 for Screening Gastritis and Gastric Cancer in a High Risk Area in Northern Iran

“…Nasrollahzadeh et al (2011) reported an AUC of 0.77 for G17 to discriminate GA. Kikushi et al (2011) also suggested G17 as good biomarker for diagnosis GA. Regarding the role of G17 pathogenesis of GC (Copps et al, 2009), further studies are warranted to assess the validity of G17 to differentiate GA/GC.…”

Gastric Damage and Cancer-Associated Biomarkers in Helicobacter pylori-Infected Children

“…It is responsible for initiating gastric acid release in the stomach in response to stimulus. During gastric cancer development, atrophic gastritis and hypergastrinemia have been proposed to be critical factors for both diffuse type and intestinal types of GC (reviewed in Waldum et al, 2017), by stimulating cell proliferation and other mechanisms not completely elucidated (Copps et al, 2009;Smith et al, 2017;Waldum et al, 2017). In children, serum gastrin and gastrin 17 have been reported to be overexpressed in H. pylori infected children in five studies included in this review (Kato et al, 2004;Maciorkowska et al, 2006;Plonka et al, 2006;Czaja et al, 2008;Guariso et al, 2009).…”