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Query: UNIPROT:P01350 (gastrin)
 9,683 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Growth factors coordinately regulate a variety of different genes to stimulate cellular proliferation. In the stomach, gastrin, epidermal growth factor (EGF), and transforming growth factor-alpha all mediate gastric mucosal homeostasis by promoting cell renewal. We have previously shown that EGF and phorbol esters stimulate the human gastrin promoter through a novel GC-rich DNA element 5'-(68)GGGGCGGGGTGGGGGG-53 called gERE (gastrin EGF response element). In this report, we show that three factors bind to this element, the transcription factor Sp1 and two fast migrating complexes designated gastrin EGF response proteins (gERP 1 and 2). To understand how these factors bind and confer EGF responsiveness, mutations of gERE were tested in vitro for protein binding and in vivo for promoter activation. Both gel shift assays and UV cross-linking studies revealed that the factors bind to overlapping domains, Sp1 to the 5' half-site and gERP 1 and 2 to the 3' half-site. Placing either the 5' or 3' mutations upstream of a minimal gastrin promoter abolished EGF induction. Therefore both the 5' and 3' domains were required to confer EGF induction. Collectively, these results demonstrate that complex interactions between Sp1 and other factors binding to overlapping gERE half-sites confer EGF responsiveness to the gastrin promoter.
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PMID:Epidermal growth factor stimulation of the human gastrin promoter requires Sp1. 789 Jul 69

The mechanism of regulation of mucus production in the gastric mucosa remains unclear. Recently, we established a gastric surface mucous cell line GSM06, which produces periodic acid-Shiff (PAS)-positive glycoconjugate (mucus) layers on the cell surface, from transgenic mice harboring a temperature-sensitive simian virus 40 large T-antigen gene. In this study, GSM06 cells were examined for its production of PAS-positive glycoconjugate layers to acid secretagogues and growth factors. The cells were cultured at nonpermissive temperature (39 degrees C) for 3-18 days and stained with PAS. Insulin (1-30 microg/ml; 0.29-8.6 microM) time- and dose-dependently increased production of glycoconjugates on the cell surface. When glycoconjugate layers produced by stimulation of insulin (3-30 microg/ml; 0.86-8.6 microM) were removed from the cell surface of GSM06 cells by a mild trypsin treatment, PAS-positive materials were remarkably decreased (day 18). In addition, morphological findings indicate that a high concentration of insulin (30 microg/ml; 8.6 microM) produced thick PAS-positive glycoconjugate layers just like normal gastric surface mucosa on the cell surface on day 18. In contrast, histamine (0.1-100 microM), carbachol (0.1-100 microM), gastrin-17 (0.1-100 nM), epidermal growth factor (0.01-10 ng/ ml; 1.7-1,700 pM), transforming growth factor-alpha (0.01-10 ng/ml; 1.8-1,800 pM), and fetal bovine serum (1-10%) did not increase glycoconjugate production. These findings suggest that insulin is a stimulator of glycoconjugate production, and stimulates production of glycoconjugate layers on the cell surface in the gastric surface mucous cell line GSM06.
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PMID:Insulin stimulates production of glycoconjugate layers on the cell surface of gastric surface mucous cell line GSM06. 901 7

Epidermal growth factor (EGF) and transforming growth factor-alpha (TGF-alpha) inhibit gastric acid secretion both in vivo and in vitro. Previous studies have indicated that EGF and TGF-alpha bind to the same EGF/TGF-alpha receptor. Nevertheless, we and others have previously demonstrated that inhibition of acid secretion by these growth factors requires concentrations of the peptides that are 10-fold higher than those necessary for induction of mitogenesis. Therefore, we have sought to investigate whether gastric parietal cells may possess a second EGF/TGF-alpha receptor class. Two systems were studied: First, [125I]TGF-alpha was cross-linked to the receptor in isolated rabbit parietal cell membranes, and labeled species were resolved on SDS-PAGE. Second, acid secretion was evaluated in pylorus-ligated waved-2 mutant mice, which carry a disabling point mutation in their classical EGF/TGF-alpha receptor. In isolated parietal cells, [125I]TGF-alpha was cross-linked into a single species of 170 kDa. Cross-linking was inhibited in the presence of unlabeled TGF-alpha with an IC50 of 80 nM. In the pylorus-ligated mice, control littermate mice demonstrated a dose-dependent inhibition of acid secretion by EGF with an IC50 of 20 micrograms/kg. In contrast, EGF had no inhibitory effect on acid secretion in waved-2 mice at concentrations up to 100 micrograms/kg. No alterations in parietal cell or gastrin cell numbers were observed. These results in both isolated rabbit parietal cells and waved-2 mice support the existence of only a single class of EGF/TGF-alpha receptors in parietal cells. Differences in growth factor affinity are likely due to the modification of the receptor or one of its coordinate regulators.
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PMID:Inhibition of parietal cell acid secretion is mediated by the classical epidermal growth factor receptor. 920 Oct 84

The present study was designed to investigate whether heparin-binding epidermal growth factor-like growth factor and its related peptides are expressed in response to gastrin in rat stomach. Rat gastrin-17I (2.5 nmol/kg/hour) or gastrin-17I plus gastrin receptor antagonist, L-740,093 (2.0 mg/kg/hour), was injected intravenously into male Sprague-Dawley rats. RNA was extracted from oxyntic mucosa, and heparin-binding epidermal growth factor-like growth factor and related peptide gene expression was estimated using a ribonuclease protection assay. The level of transforming growth factor-alpha mRNA did not change at any time point during the experiment. In contrast, the levels of heparin-binding epidermal growth factor-like growth factor and amphiregulin mRNA were significantly increased within 3 hours following gastrin infusion and reached maximum levels 6 and 12 hours later, respectively. Continuous infusion of gastrin significantly increased oxyntic mucosal proliferation. Gastrin receptor antagonist significantly inhibited gastrin-induced heparin-binding epidermal growth factor-like growth factor and amphiregulin gene expression and gastrin-induced oxyntic mucosal proliferation. These findings indicate that heparin-binding epidermal growth factor-like growth factor and amphiregulin genes are induced by gastrin and that they play a role in the trophic action of gastrin on oxyntic mucosa.
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PMID:Induction of heparin binding epidermal growth factor-like growth factor and amphiregulin mRNAs by gastrin in the rat stomach. 920 88

In adult rats islet cell neogenesis can be stimulated by partial duct ligation. Duct to islet cell differentiation is thought to be regulated by growth factors such as gastrin and transforming growth factor-alpha (TGF alpha). To test this hypothesis, we examined the expression of gastrin and TGF alpha at the mRNA and protein level in pancreatic tissue following partial duct ligation. Pancreatic specimens were investigated on days 3, 5, 7 and 14 after duct ligation by means of non-isotopic in situ hybridization, immunocytochemistry and Western blotting. Gastrin mRNA was strongly expressed in newly developed duct-like cell structures in the ligated tail portion of the pancreas before the period of pronounced islet cell neogenesis (days 5 and 7), and immunostaining for gastrin peptides was positive at days 5-7. In the non-ligated head portion and in control pancreases, gastrin was not expressed. Expression of TGF alpha was found to be increased in the ligated tail portion of the pancreas on day 3 and particularly on day 5, while there was no enhanced signal in the non-ligated part. Western blotting revealed two different TGF alpha isoforms (18 kDa and 42 kDa) in the ligated tail part and three isoforms (18 kDa, 24 kDa and 42 kDa) in the non-ligated head part and in untreated pancreases. The induction of gastrin and TGF alpha expression preceded the peak in the bromodeoxyuridine pulse labelling index of beta cells, known from a previous study to occur on day 7. We conclude that pancreas duct ligation induces the overexpression of gastrin and TGF alpha in the first days following ligation. Since ductal cells are known to give rise to endocrine cells after duct ligation, gastrin and TGF alpha may play a role as growth factors in islet neogenesis.
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PMID:Expression of gastrin and transforming growth factor-alpha during duct to islet cell differentiation in the pancreas of duct-ligated adult rats. 926 82

Of the two known forms of intestinal somatostatin, somatostatin-28 (S28) and S14, S28 predominates in the distal mucosa, whereas S14 is localized in the foregut. Although S14 release has been well studied, little is known about the factors regulating secretion of S28 from the intestine. Therefore, fetal rat intestinal cultures, which have been previously demonstrated to synthesize and secrete predominantly S28, were treated with potential nutrient, neuromodulator/transmitter, and peptide secretagogues (n = 4-6/experiment). Oleic acid dose dependently stimulated the release of somatostatin-like immunoreactivity (SLI) to 272 +/- 81% of the control value at 1.5 x 10(-4) M (P < 0.01). Gel permeation analysis (n = 3) demonstrated that this increment was accounted for not only by an increase in the release of S28, but also by an increase in that of S14, such that the secretion of both peptides was increased in parallel. Of the neuromodulators tested, only the enteric peptide gastrin-releasing peptide stimulated intestinal SLI secretion, to 386 +/- 60% of the control value at 10(-6) M (P < 0.001); similar to oleic acid, the effects on S28 and S14 were equivalent. Galanin, vasoactive intestinal peptide, bethanechol, and epinephrine did not affect SLI release. The duodenal hormone secretin also stimulated SLI release to 310 +/- 78% of the control value at 10(-6) M (P < 0.001); however, secretin caused a preferential release of S14 over that of S28 (S14, 7.8 +/- 2.8-fold; S28, 1.5 +/- 0.1-fold). In contrast, gastrin, cholecystokinin, glucose-dependent insulinotropic peptide, neurotensin, peptide YY, epidermal growth factor, and transforming growth factor-alpha had no effect on intestinal SLI release. Thus, luminal nutrients and neuro/endocrine peptides exert differential effects on S28 release from the rat intestine compared with those on S14. These findings implicate S28 as a distinct regulatory peptide in the physiological setting.
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PMID:Nutrient and peptide regulation of somatostatin-28 secretion from intestinal cultures. 942 9

Neuroendocrine proliferation of gastric mucosa is commonly encontered in routine gastric biopsies and is an indirect effect of modern drugs suppressing acid secretion. The process is virtually circumscribed to the ECL cell, the most common endocrine cell of the oxyntic mucosa, and is dependent on the trophic effect of the concomitant hypergastrinemia in most cases. It starts in the form of hyperplastic lesions that in some cases evolves into dysplasia and neoplasia. Gastrin has promoting but not transforming properties for such ECL cell tumour induction. Proven or potential transforming factors include the allelic loss of the MEN-1 suppressor gene at 11q13, the still unknown factor(s) associated with atrophic corporal gastritis in which overexpression of BCL-2 likely plays a favouring role by prolonging ECL exposure to mitogens, and agents with still unclarified role, such as basic fibroblast growth factor, human chorionic gonadotropin-alpha and transforming growth factor-alpha. Gastric neuroendocrine tumours independent of the trophic effect of gastrin are less frequent but more malignant. Their pathogenesis and precursor lesions are ignored.
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PMID:Neuroendocrine proliferation in the gastric mucosa: biological behaviour and management. 947 60

In Fischer 344 rats, induction of gastric mucosal proliferative activity, whether the result of aging or injury or occurring after administration of epidermal growth factor, gastrin, or bombesin, is associated with a rise in tyrosine kinase activity and tyrosine phosphorylation of several mucosal proteins, including a protein with a molecular mass of 53-55 kDa. We hypothesized that this phosphotyrosine membrane protein (referred to as pp55) may play a role in regulating gastric mucosal cell proliferation and differentiation. Purification and subsequent immunoprecipitation studies now show that pp55 is a tyrosine kinase. In addition, the enzyme activity in the gastric mucosa is found to be fourfold higher in aged rats than in young rats. Incubation of gastric mucosal membranes with transforming growth factor-alpha (2 x 10(-8) M) stimulates tyrosine kinase activity of pp55. Immunolocalization studies reveal that pp55 immunoreactivity is predominantly present in mucous cells that are located just above the proliferative zone and spasmolytic peptide-immunoreactive mucous neck cells. Tyrosine kinase activity as well as expression of pp55 are also greatly increased in the gastric mucosa after hypertonic saline-induced injury, a condition that results in stimulation of surface mucosal cell proliferation and differentiation. Our current data suggest that pp55 is a tyrosine kinase, likely localized to pre-surface cells. The presence of pp55 in pre-surface mucous cells and the expression and tyrosine kinase activity of this protein, which can be stimulated during mucosal cell proliferation and differentiation, strongly suggest a role for pp55 in differentiation of gastric surface mucous cells.
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PMID:Localization and significance of pp55, a gastric mucosal membrane protein with tyrosine kinase activity. 961 67

We have previously demonstrated that in Mastomys species proliferation of gastric enterochromaffin-like (ECL) cells is predominantly regulated by gastrin and by transforming growth factor-alpha (TGF-alpha) in the naive and neoplastic state, respectively. In this study we examined whether these intracellular mitogenic responses are mediated by polyamines and ornithine decarboxylase (ODC), the rate-limiting enzyme for polyamine biosynthesis. An ECL cell preparation of high purity was used to measure the effect of the polyamine derivatives putrescine, spermidine, and spermine on DNA synthesis by bromodeoxyuridine uptake. Both putrescine and spermidine augmented gastrin-stimulated, but not basal, DNA synthesis in naive cells. This proliferative response correlated with an increase in ODC activity that was partially inhibited (20%) by difluoromethylornithine (DFMO), an inhibitor of ODC (IC50, 30 pM). In contrast, all polyamines increased both basal and TGF-alpha-stimulated DNA synthesis as well as ODC activity in tumor ECL cells. DFMO completely inhibited the proliferative response of TGF-alpha (IC50, 3 pM). Thus polyamine biosynthesis is involved in proliferation of ECL cells and in particular the mitogenesis of tumor cells, suggesting a role for this pathway in the regulation of ECL cell transformation.
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PMID:A polyamine pathway-mediated mitogenic mechanism in enterochromaffin-like cells of Mastomys. 968 65

Enterochromaffin-like (ECL) cells are histamine-containing endocrine cells in the gastric epithelium that show increased density during chronic atrophic gastritis. The current study determined cell number and apoptosis of isolated rat ECL cells in response to several growth factors. Isolated ECL cells from fundic mucosa (enrichment >90%) were grown in serum-free medium over 2-5 days. Cell number was determined by mitochondrial formazan production; apoptosis was measured by Tdt-mediated dUTP nick end labeling reaction and DNA fragmentation-based enzyme-linked immunosorbent assay. Immunocytochemistry and RT-PCR demonstrated the presence of epidermal growth factor receptor, neuronal growth factor receptor (type 1), and fibroblast growth factor (FGF) receptor (type 1). Gastrin (EC50, approximately 2 pM), transforming growth factor-alpha (TGF alpha; 10-30 ng/ml), and basic FGF (bFGF; 1-10 ng/ml) increased the total number of cultured ECL cells. bFGF augmented the gastrin (1 pM)-induced response. Beta-neuronal growth factor (10 ng/ml) and bFGF (2 ng/ml) decreased the programed death of ECL cells. Interleukin-1beta (100 pg/ml, 24 h) stimulated apoptosis 2- to 3-fold in ECL cells, and simultaneous incubation with TGF alpha (20 ng/ml) or bFGF (2 ng/ml) significantly inhibited this effect. ECL cells express specific receptors for gastrin, epidermal growth factor, neuronal growth factor, and FGF. bFGF prolonged ECL cell survival by inhibiting spontaneous apoptosis. Our data further indicate that TGF alpha and bFGF increase ECL cell number by inhibiting cytokine-induced programed cell death.
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PMID:Growth factor effects on apoptosis of rat gastric enterochromaffin-like cells. 975 22


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