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)

A combination of several enzymes, RNase-T1, nuclease S1, T4-polynucleotide kinase and T4-RNA ligase were used to prepare and modify different fragments of yeast tRNAAsp (normal anticodon G U C). This allowed us to reconstitute, in vitro, a chimeric tRNA that has any of the four bases G, A, U or C, as the first anticodon nucleotide, labelled with (32p) in its 3' position. Such reconstituted (32p) labelled yeast tRNAAsp were microinjected into the cytoplasm or the nucleus of the frog oocyte and checked for their stability as well as for their potential to work as a substrate for the maturation (modifying) enzymes under in vivo conditions. Our results indicate that the chimeric yeast tRNAsAsp were quite stable inside the frog oocyte. Also, the G34 was effectively transformed inside the cytoplasm of frog oocyte into Q34 and mannosyl-Q34; U34 into mcm5s2U and mcm5U. In contrast, C34 and A34 were not transformed at all neither in the cytoplasm nor in the nucleus of the frog oocyte. The above procedure constitutes a new approach in order to detect the presence of a given modifying enzyme inside the frog oocyte; also it provides informations about its cellular location and possibility about its specificity of interaction with foreign tRNA.
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PMID:Enzymatic replacement in vitro of the first anticodon base of yeast tRNAAsp: application to the study of tRNA maturation in vivo, after microinjection into frog oocytes. 628 19

To investigate further the presence of an autocrine proliferative loop involving gastrin in colorectal carcinomas and to clarify the receptor responsible, 102 human colorectal carcinomas and 10 hepatic metastases were investigated for the expression of the genes encoding gastrin, the gastrin/CCK-B receptor and the gastrin/CCK-C receptor. Levels of RNA expression were assayed by RNase protection assay. In addition, gastrin/CCK receptors on crude membranes of tumour tissue were assayed by radioligand binding. High-affinity gastrin/CCK-B receptors were not detected in any of the carcinomas investigated, whereas in 36% low-affinity binding was observed, consistent with the expression of the gastrin/CCK-C receptor. RNase protection assay detected the RNA for the gastrin/CCK-B receptor in 11% of the carcinomas investigated, whereas the RNA for the gastrin/CCK-C receptor was demonstrated in 75% and the RNA for gastrin in 86% of the carcinomas investigated. These results confirm the recent demonstration of progastrin fragments in colorectal carcinomas. One possible explanation for progastrin expression is that such progastrin fragments may participate in an autocrine proliferative loop. The receptor involved in this loop is more likely to be the low-affinity gastrin/CCK-C receptor rather than the gastrin/CCK-B receptor, which is rarely expressed in colorectal carcinomas.
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PMID:Expression of gastrin, gastrin/CCK-B and gastrin/CCK-C receptors in human colorectal carcinomas. 759 30

Gastrin is transcriptionally responsive to EGF stimulation (Merchant et al., 1991, Mol. Cell. Biol., 11:2686-2696). Consequently, we hypothesized that previously recognized gastrin autocrine loops (Hoosein et al., 1990, Exp. Cell. Res., 186:15-21), might be controlled by autocrine TGF alpha in human colon carcinoma cells. Therefore, we examined the interaction between these two autocrine growth factors in two colon carcinoma cell lines which utilize TGF alpha. The FET cell line requires exogenous TGF alpha/EGF for optimal growth and has a classical TGF alpha autocrine loop which is disrupted by TGF alpha or epidermal growth factor receptor (EGFr) antibodies. The HCT 116 cell line is not dependent on exogenous TGF alpha/EGF and exhibits a nonclassical TGF alpha autocrine loop which is not disrupted by neutralizing antibodies to either TGF alpha itself or the EGFr. Basal gastrin mRNA production is significantly higher in HCT 116 than FET as measured by RNase protection assay. In the FET cells, exogenous EGF stimulates gastrin mRNA production but not in HCT 116. When the TGF alpha autocrine loop in HCT 116 is disrupted by constitutive expression of antisense TGF alpha mRNA, the gastrin mRNA level is significantly repressed. In xenografts derived from these antisense clones, TGF alpha reverted to high expression, and the gastrin mRNA level was again increased. This interaction between the strong TGF alpha loop in HCT 116 and the gastrin autocrine loop may confer a growth advantage to these colon cells. Such interactions between growth factors may promote enhanced tumorigenicity to transformed cells with these strong, nonclassical autocrine loops.
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PMID:Regulation of autocrine gastrin expression by the TGF alpha autocrine loop. 782 34

Gastrin, produced in the G-cells of the gastric antrum and regulating acid secretion in the stomach, also acts as a trophic factor in the gastrointestinal tract. Because of its possible role in colon cell proliferation and differentiation, evidence for its presence in normal colorectal mucosa and adenocarcinoma was sought. Utilizing tumors and matched normal mucosa from 26 patients, mature gastrin and progastrin were studied by immunohistochemistry. In normal colonic mucosal crypts, occasional cells stained concordantly for gastrin, progastrin, and chromogranin A, suggesting that they are of neuroendocrine origin. Adenomatous polyps stained neither for gastrin nor chromogranin A. In 22 of 23 adenocarcinomas, more than 50% of tumor cells stained for gastrin and progastrin. The expected gastrin transcript was demonstrable by polymerase chain reaction and RNase protection in tumors and by polymerase chain reaction in normal mucosa. Its identity was confirmed by sequencing the polymerase chain reaction product. A larger transcript containing Intron II was present in both cancers and normal mucosa but was barely discernible in the gastric antrum. Aberrant expression of gastrin may contribute to deregulated proliferation of many colorectal carcinomas.
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PMID:Expression of the gastrin gene in the normal human colon and colorectal adenocarcinoma. 850 33

Recent studies have suggested that cholecystokinin (CCK) receptors may play a role in the development and growth of pancreatic cancers. We detected the expression of mRNA encoding CCK-A and CCK-B receptors in eight human pancreatic tumour cell lines using reverse transcription-polymerase chain reaction (RT-PCR), but not by RNase protection assays. The K-ras gene, which can be activated by G-coupled protein receptors such as CCK receptors, was mutated in codon 12 in five of the cell lines. In addition, Mia PaCa-2 pancreatic cancer cells did not respond to CCK or gastrin in cell proliferation or focal adhesion kinase (FAK) phosphorylation assays. In contrast, mouse NIH3T3 fibroblasts transfected with human CCK-B receptor (NIH3T3CCK-BR) showed increased proliferation and phosphorylation to the peptides. Also, radioligand binding studies indicated that Mia PaCa-2 cells had approximately 12.5-fold less CCK-B receptors than NIH3T3CCK-BR. Our results suggest that in Mia PaCa-2 cells, CCK receptors may not play a crucial role in supporting cell growth.
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PMID:Cholecystokinin receptors in human pancreatic cancer cell lines. 984 31

The murine anti-bombesin monoclonal antibody, 2A11, has been demonstrated to inhibit growth of some small-cell lung cancer (SCLC) cells in nude mice xenografts and in a clinical trial. To determine if the expression of bombesin-like peptides (BLP) and their receptors (GRP-R and NMB-R) correlate with an in vitro response to 2A11, we measured these parameters in seven SCLC cell lines. Gastrin releasing peptide (GRP) mRNA was detected in three of seven cell lines (NCI-H69, NCI-H345, NCI-H510) and neuromedin B (NMB) mRNA was detected in all seven lines using an RNase protection assay (RPA). Immunoreactive BLP was detected in the cell pellets of all lines (range 0.11-59.90 pmol/mg protein) by a solid phase GRP radioimmunoassay (RIA) using 125I-labeled 2A11. RPA detected GRP-receptor mRNA in two cell lines (NCI-H69 and NCI-H345) and NMB-receptor in three lines (NCI-H345, NCI-H510, and NCI-H660). Reverse transcriptase-PCR confirmed the presence of receptor mRNA in these lines and detected NMB-receptor in an additional three lines (NCI-H69, NCI-H82, and NCI-H187). Calcium mobilization in response to BLP stimulation was detected in the six cell lines expressing either GRP-R or NMB-R mRNA but not in NCI-N417, which had no detectable BLP-receptor. 2A11 (5 microg/ml) inhibited colony formation by 26-61% after 2 weeks in all cell lines except NCI-N417. Thus, growth inhibition by 2A11 requires the presence of at least one BLP-receptor. These findings may be useful in selecting patients with SCLC for treatment with 2A11.
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PMID:Correlation of expression of bombesin-like peptides and receptors with growth inhibition by an anti-bombesin antibody in small-cell lung cancer cell lines. 985 94

Chronic inflammation of the gastric epithelium is believed to induce mucosal changes that can eventually develop into gastric cancer. In gastrin-deficient (G-/-) mice exhibiting chronic inflammation in the hypochlorhydric stomach, we documented a prominent fundic mucous cell lineage sharing morphological similarity with preneoplastic changes reported in Helicobacter-infected mice. To study the identity and origin of this cell lineage, we screened for different gastric mucosal cell markers. The clusters of large, foamy cells stained for trefoil factor 2 (TFF2/SP), MUC6 and the lectin Griffonia Simplicifolia II (GSII), but not for the intestine-specific transcription factor Cdx2, suggested that they arise from gastric mucous neck cells. Ki67-labeled GSII-positive neck cells in Helicobacter felis-infected, but not G-/- stomachs, suggested that mucous neck cell proliferation accounted for expansion of this compartment in the H. felis model of gastritis, but not the G-/- model. Using RNase protection assays and quantitative PCR, we found that interferon gamma (IFNgamma) was the most abundant proinflammatory cytokine in the G-/- stomach. We also found that this Th1 cytokine can increase the abundance of mucous neck cells, since its infusion into mice recapitulated the appearance of these cells as observed in both G-/- and H. felis-infected mice. Using the human gastric cell line NCI-N87, we showed that IFNgamma induces the secretion of mucus and expression of MUC6, TFF2 and pepsinogen II, but not of pepsinogen I and intrinsic factor. In conclusion, our results demonstrate that inflammation, specifically the proinflammatory cytokine IFNgamma, induced expansion of the fundic mucous neck cell compartment, which likely represents both increased mucus production and cell number.
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PMID:Interferon gamma induction of gastric mucous neck cell hypertrophy. 1576 19

The gastrointestinal peptide cholecystokinin (CCK) causes the release of pancreatic digestive enzymes and growth of the normal pancreas. Exogenous CCK administration has been used in animal models to study pancreatitis and also as a promoter of carcinogen-induced or Kras-driven pancreatic cancer. Defining CCK receptors in normal human pancreas has been problematic because of its retroperitoneal location, high concentrations of pancreatic proteases, and endogenous RNase. Most studies indicate that the predominant receptor in human pancreas is the CCK-B type, and CCK-A is the predominant form in rodent pancreas. In pancreatic cancer cells and tumors, the role of CCK is better established because receptors are often overexpressed by these cancer cells and stimulation of such receptors promotes growth. Furthermore, in established cancer, endogenous production of CCK and/or gastrin occurs and their actions stimulate the synthesis of more receptors plus growth by an autocrine mechanism. Initially it was thought that the mechanism by which CCK served to potentiate carcinogenesis was by interplay with inflammation in the pancreatic microenvironment. But with the recent findings of CCK receptors on early PanIN (pancreatic intraepithelial neoplasia) lesions and on stellate cells, the question has been raised that perhaps CCK actions are not the result of cancer but an early driving promoter of cancer. This review will summarize what is known regarding CCK, its receptors, and pancreatic cancer, and also what is unknown and requires further investigation to determine which comes first, the chicken or the egg, "CCK or the cancer."
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PMID:Cholecystokinin and pancreatic cancer: the chicken or the egg? 2417 32