Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P01350 (gastrin)
 9,683 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Changes in antral and serum gastrin levels as well as gastrin (G) and somatostatin (D) cell density were examined in 4- to 16-mo-old Fischer-344 rats. In these rats, the responsiveness of the gastric mucosa to the trophic action of gastrin was also examined. It was observed that whereas serum gastrin levels declined steadily between 4 and 16 mo of age, antral gastrin levels rose sharply during this period. In the antrum of 16-mo-old rats, the density of G-cells, but not D-cells, was found to be lower than in their 4-mo-old counterparts. Thus, when D- to G-cell ratios were calculated, 16-mo-old rats revealed a 50% higher D- to G-cell ratio than the 4-mo-old animals. To assess the trophic action of gastrin, groups of 4-, 8-, and 16-mo-old rats were infused subcutaneously (osmotic minipump) with either saline or gastrin (G-17-I; 250 ng.kg-1.h-1) for 14 days. The gastric mucosa was assayed for thymidine kinase (an indicator of proliferative activity) and DNA and protein content. In the saline-infused rats, gastric mucosal thymidine kinase activity increased sharply between 4 and 16 mo of age without significantly affecting DNA or protein content (expressed as milligrams per 100 g of body weight), suggesting that the age-associated rise in proliferative activity is not accompanied by increased mucosal growth.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Gastrin: levels and trophic action during advancing age. 289 88

Antral, duodenal, and serum gastrin levels and colonic thymidine kinase activity were determined in 1- to 4-day-fasted rats and after refeeding of 4-day-fasted rats for 3-24 h. The effect of pentagastrin on colonic thymidine kinase activity was also determined. Total deprivation of food caused a drastic reduction in gastrin concentrations in serum and tissues. After 4 days of fasting, serum gastrin levels in most animals fell below the present detection limit of the assay (10-15 pg/ml), and antral and duodenal gastrin levels decreased to 15 and 50% of the respective initial fed control. After 9 and 24 h of refeeding, gastrin concentration in serum and antrum had increased to about 35% of the initial fed level. On the other hand, refeeding for 3-24 h produced no significant change in duodenal gastrin concentration. Fasting for 1-4 days resulted in a 60-70% reduction in colonic thymidine kinase activity, compared to the initial fed control. Refeeding caused a prompt stimulation in the enzyme activity, which after 6 h was found to be 72% above the 4-day-fasted group. Daily injection of pentagastrin, at doses between 125 and 500 micrograms/kg, during a 4-day fasting period resulted in a significant stimulation in colonic thymidine kinase activity, compared to the saline-treated control. The maximal stimulation of an enzyme activity 90% higher than in the saline control was attained with a pentagastrin dose of 125 micrograms/kg. Higher doses decreased the maximal stimulatory effect of pentagastrin.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Effects of fasting and refeeding on antral, duodenal, and serum gastrin levels and on colonic thymidine kinase activity in rats. 670 92

The growth of the human gastric cancer cell line HGT-1 is regulated by a gastrin-like peptide through an autocrine process. In order to analyse the mechanism of action of this peptide, a study at different steps of the cell cycle was considered; so, a blocking of this cell line by thymidine or hydroxy-urea was studied by cytofluorimetry. In normal growth conditions in 10% FCS medium, 57% of the cells were in G0/G1 phase and 31% in S phase. A treatment with 2 mM hydroxy-urea followed by 4 hours in 10% FCS medium led to 85% of the cells in S phase. By successive treatments with thymidine and hydroxy-urea followed by 1 hour in 10% FCS medium, 2 peaks of S phase corresponding to 86% of the cells were observed; after 24 hours, cells were distributed as found for the unconfluent cell line, whatever the treatment. On the other hand, the thymidine kinase activity of unconfluent cells which was relatively elevated as compared to other cell lines (278 mU/mg protein), was increased by synchronisation with hydroxyurea followed by 1 hour in 10% SVF medium (338 mU/mg protein); after 8 hours in 10% FCS medium, this activity decreased at the value observed for cells treated with thymidine followed by 1 hour in 10% FCS medium (214 mU/mg protein). In conclusion, a synchronisation either by thymidine or by hydroxy-urea, led to a blocking of the HGT-1 cell line at different steps of the cell cycle, leading to a better knowledge of its autocrine growth regulation.
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PMID:[Study of S phase synchronization of the human gastric cancer line HGT-1]. 806 18

Transcriptional regulation of the human histidine decarboxylase (HDC) gene by gastrin and the phorbol ester phorbol 12-myristate 13-acetate (PMA) was studied using transient transfection of human HDC promoter-luciferase constructs in a human gastric carcinoma cell line (AGS-B) that expresses the human cholecystokinin-B/gastrin receptor. The transcriptional activity of the human HDC promoter was stimulated 3-4-fold by gastrin and 13-fold by PMA, effects that could be blocked by down-regulation or antagonism of protein kinase C. 5'- and 3'-deletion analysis demonstrated that the sequence responsible for gastrin- and PMA-stimulated transactivation (gastrin response element (GAS-RE)) was located in a region (+2 to +24) downstream of the transcriptional start site (+1) in the human HDC promoter and contained a palindrome (5'-CCCTTTAAATAAAGGG-3'). When ligated upstream of the herpes simplex virus 1 thymidine kinase promoter, a single copy of the GAS-RE was sufficient to confer responsiveness to gastrin and PMA. Electrophoretic mobility shift assays with specific competitors and factor-specific antibody supershifts showed that the labeled GAS-RE bound a novel nuclear factor(s). In addition, both gastrin and PMA increased binding of this factor to the GAS-RE. Hence, the palindromic GAS-RE site is sufficient to explain the gastrin/PMA responsiveness of the human HDC promoter and appears to bind a novel transcription factor.
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PMID:The human histidine decarboxylase promoter is regulated by gastrin and phorbol 12-myristate 13-acetate through a downstream cis-acting element. 866 34

Chromogranin A (CgA) is a multifunctional acidic protein that in the stomach is expressed predominantly in enterochromaffin-like cells (ECL cells) where it is regulated by gastrin. In order to investigate the transcriptional response of the mouse CgA (mCgA) promoter to gastrin stimulation, we studied a 4.8-kilobase mCgA promoter-luciferase reporter gene construct in transiently transfected AGS-B cells. 5'-Deletion analysis and scanning mutagenesis of mCgA 5'-flanking DNA showed that a Sp1/Egr-1 site spanning -88 to -77 base pairs (bp) and a cyclic AMP-responsive element (CRE) at -71 to -64 bp are essential for gastrin-dependent mCgA transactivation. Gastrin stimulation increased cellular Sp1 protein levels and Sp1-binding to the mCgA -88 to -77 bp element, as well as binding of CREB to its consensus motif at -71 to -64 bp. Gastrin also stimulated CREB Ser-133 phosphorylation, and abundance of cellular CREB protein levels. Overexpression of either Sp1 or phosphorylated CREB transactivated the mCgA promoter dose dependently, while coexpression of both transcription factors resulted in an additive mCgA promoter response. mCgA -92 to -64 bp, comprising the Sp1/Egr-1 site and the CRE motif, conferred gastrin responsiveness to a heterologous thymidine kinase promoter system, and therefore functions as a "true" enhancer element. This report demonstrates that Sp1 and CREB mediate CCK-B/gastrin receptor-dependent gene regulation, and that the effect of gastrin on the CgA gene is brought about by cooperative action of both transcription factors.
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PMID:Sp1 and CREB mediate gastrin-dependent regulation of chromogranin A promoter activity in gastric carcinoma cells. 985 54

In the accompanying study, we show how retroviral tropism can be redirected by insertion of short peptide ligands at multiple locations in envelope. Here we use this approach to selectively target and destroy human cancer cells. Many cancer cells overexpress specific cell surface receptors. We have generated Moloney murine leukemia virus (MLV) envelope derivatives bearing short peptide ligands for gastrin-releasing protein (GRP) and human epidermal growth factor receptors. Pseudotyped viruses containing these chimeric envelope derivatives selectively transduce human cancer cell lines that overexpress the cognate receptor. A retrovirus targeting the GRP receptor can deliver the thymidine kinase gene to human melanoma and breast cancer cells, which are killed by the subsequent addition of ganciclovir. Collectively, our results demonstrate that short peptide ligands inserted at appropriate locations in MLV envelope can selectively target retroviruses to human cancer cells and deliver a therapeutically relevant gene.
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PMID:Selective targeting and inducible destruction of human cancer cells by retroviruses with envelope proteins bearing short peptide ligands. 1188 81

The insulinoma-associated 1 (INSM1) gene is expressed exclusively during early embryonal development, but has been found re-expressed at high levels in neuroendocrine tumors. The regulatory region of the INSM1 gene is therefore a potential candidate for regulating expression of a therapeutic gene in transcriptionally targeted cancer gene therapy against neuroendocrine tumors. We analyzed expression of a reporter gene from a 1.7 kb region of the INSM1 promoter in a large number of small-cell lung cancer (SCLC) cell lines. This INSM1 promoter region showed very high levels of expression in most of the SCLC cell lines and expression was absent in cell lines of non-neuroendocrine origin. Inclusion of the general transcriptional enhancer from SV40 compromised the specificity of the promoter and did not enhance transcription in most of the SCLC cell lines. For comparison, the region of the gastrin releasing peptide (GRP) previously suggested for SCLC gene therapy was analyzed in a similar manner. High expression was observed for a number of cell lines, but unlike for the INSM1 promoter, reporter gene expression from the GRP promoter did not correlate to the relative GRP mRNA levels, demonstrating that this region may not contain all necessary regulatory elements. Expression of the suicide gene herpes simplex virus thymidine kinase (HSV-TK) from the INSM1 promoter in combination with treatment with the prodrug ganciclovir (GCV) caused a significant increase in GCV sensitivity specifically in INSM1-expressing cell lines. The INSM1 promoter is therefore a potential novel tool for transcriptionally targeted gene therapy for neuroendocrine tumors.
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PMID:The insulinoma-associated 1: a novel promoter for targeted cancer gene therapy for small-cell lung cancer. 1605 25