Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0024623 (gastric cancer)
 36,219 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

K-sam was first identified as a gene amplified in the stomach cancer cell line KATO-III. The size of the major transcript of the K-sam gene was 3.5 kilobases in KATO-III cells, and we have previously shown that K-sam encodes a receptor tyrosine kinase that belongs to the heparin-binding growth factor receptor, or fibroblast growth factor receptor, gene family. The K-sam gene expresses multiple sizes of mRNAs in brain tissue, the immature teratoma cell line NCC-IT, and KATO-III. RNA blot analyses with a variety of K-sam probes indicate that there are at least four classes of K-sam mRNAs. Three types of K-sam cDNAs in addition to the previously reported type of K-sam cDNA were isolated, and their nucleotide sequences encode a full-length transmembrane receptor, a secreted receptor with a tyrosine kinase domain, and a secreted receptor without a tyrosine kinase domain.
 ...
PMID:K-sam gene encodes secreted as well as transmembrane receptor tyrosine kinase. 131 74

K-SAM gene was originally isolated as an amplified gene in a stomach cancer cell line by in-gel DNA renaturation method. K-SAM encodes a membrane receptor with tyrosine kinase and is often amplified in poorly differentiated type of stomach cancer, while c-ERBB-2 is often amplified in well differentiated type of stomach cancer. There are several forms of K-SAM mRNAs which are generated by alternative splicing, and two types of K-SAM protein without transmembrane region. The ligand of K-SAM is considered to be growth factor(s) belonging to fibroblast growth factor (FGF) or heparin binding growth factor (HBFG) family. We have also frequently found amplification of HST-1 or HSTF1 gene in esophageal cancer. HST-1 gene, originally found as a transforming gene, is located on human chromosome 11q13, and it locates 35 kbp apart from its related gene, INT-2. Neither of the genes was expressed even in cancer cells with the co-amplification. By cosmid walking, we have identified at least two genes, designated tentatively as EXP1 and EXP2, on the same amplicon as HST-1 and INT-2, and the mRNAs for EXP1 and EXP2 genes were increased in amounts proportional to the degree of amplification.
 ...
PMID:Biological significance of gene amplification in carcinogenesis. 184 51

DNAs from 15 samples of primary stomach cancer were transfected into NIH3T3 cells. Five stomach cancer DNAs (ST1, ST3, ST6, ST7, and ST15) showed transforming activity. These transformations were caused by human cancer DNAs since human Alu repetitive sequences were detected in transformant DNAs. DNAs from transformants were screened with 22 oncogene probes available, including Ha-ras, Ki-ras, and N-ras. However, these probes did not hybridize with any human DNA in transformants. A transforming gene was cloned from an ST6-derived transformant, which turned out to be hst oncogene. By use of a probe derived from the cloned hst gene, it was shown that additional two transformants (ST7- and ST15-derived) also harboured human hst. Here I report molecular cloning of another transforming gene from an ST1-derived transformant. The transforming gene was cloned by cosmid rescue method being tagged with pSV2-gpt. The normal counterpart of the transforming gene was also cloned from a genomic phage library of human placenta DNA. Surprisingly, the transforming gene was not colinear with the placenta DNA, but was generated by the recombination of two separate genes. Comparison of the restriction maps of these genes with those of reported oncogenes showed that 3'-half of the cloned transforming gene was colinear with the 3'-half of the ret oncogene, which encodes tyrosine kinase domain. It was suggested that this gene was activated by DNA rearrangement upon transfection, placing a transcriptionally active promoter on upstream of the kinase domain. Among 4 primary transformants derived from ST1 two did not have human ret oncogene, indicating that other transforming genes were involved in these transformation events.
 ...
PMID:[ret gene from a human stomach cancer]. 324 71

c-erbB3 product is moderately expressed in gastric mucosa, especially in parietal cells. Northern blot analysis revealed that 6.2-kb c-erbB3 transcript was expressed in all gastric cancer cell lines examined, and that 1.4-kb c-erbB3 transcript was expressed as highly as 6.2-kb transcript in MKN45 cells. erbB3-S cDNA, corresponding to 1.4-kb c-erbB3 transcript, was cloned by rapid amplification of cDNA ends. Sequence analysis of erbB3-S cDNA showed that this 1.4-kb c-erbB3 mRNA encoded a secreted receptor. Analysis of partial genomic structure of c-erbB3 gene revealed that the exon specific to secreted receptor was identical with the 5' portion of the intron in c-erbB3 gene. c-erbB3 gene encodes secreted as well as transmembrane receptor tyrosine kinase due to alternative splicing.
 ...
PMID:c-erbB3 gene encodes secreted as well as transmembrane receptor tyrosine kinase. 768 62

For identification of the protein-tyrosine kinases that are expressed in embryo stomach and gastric cancer, a 16-day rat embryo stomach and two human gastric cancer cDNA expression libraries were screened with an anti-phosphotyrosine antibody. Eight cDNAs encoding protein-tyrosine kinase were isolated, and Northern blot analysis revealed that five out of eight clones were highly expressed in rat embryo stomach, but not in adult rat stomach. From nucleotide sequence analysis, these five cDNAs were identified as elk, erk, esk, TTK and fyn, respectively. We report here that the expression levels of two families of receptor type tyrosine kinase genes, elk/erk and esk/TTK are developmentally regulated in rat stomach and highly expressed in human gastric cancer tissues. These findings suggest that elk/erk and esk/TTK genes play important roles in embryonic development and carcinogenesis of the stomach.
 ...
PMID:Identification of protein-tyrosine kinase genes preferentially expressed in embryo stomach and gastric cancer. 768 22

Bombesin (BBS) and its mammalian equivalent, gastrin-releasing peptide (GRP), exhibit diverse biological functions, including that of a neurotransmitter, a regulator of gastrointestinal hormone release, and a trophic factor for various normal and neoplastic tissues. Bombesin stimulates the growth of normal cells of the stomach, pancreas, and bronchial epithelium as well as cells in breast cancer, gastrinoma, and small cell lung cancer. The purpose of this study was to determine whether BBS regulates the growth of a human gastric cancer cell line (SIIA) in vitro, and if so, to examine the mechanisms of signal-transduction that are involved. We found that BBS stimulated the growth of SIIA cells in vitro. The GRP receptor antagonists, BIM 26189 and BIM 26226, had no effect on growth of SIIA cells. Although these antagonists blocked the BBS-induced increase of [Ca2+]i, they failed to block the growth-stimulatory effect of BBS. BBS stimulated intracellular tyrosine phosphorylation of multiple proteins, with a predominant protein of apparent molecular weight of 125 kDa. Inhibition of intracellular tyrosine kinases by tyrphostin blocked the growth-stimulatory effect of BBS on SIIA cells. These results indicate that BBS exerts its trophic effect on SIIA cells through a receptor(s) linked to tyrosine kinase pathway, but not to the phospholipase C (PLC) pathway.
 ...
PMID:Bombesin stimulates the in vitro growth of a human gastric cancer cell line. 796 32

AGS human gastric cancer cells were characterized to possess EGF receptors. Scatchard analysis revealed a half saturation constant of 0.6 nM and 9000 receptors per cell. Exogenously added EGF stimulated gastric cancer cell growth in a dose-dependent manner with a maximum effect of +38% at 10 nM EGF. Inhibition of the EGFR-associated tyrosine kinase by genistein and the tyrphostins RG-13022, RG-14620 and RG-50864 resulted in a dose-dependent growth inhibition with half maximal inhibition at 10 microM, 7 microM and 23 microM, respectively. EGF mediated growth stimulation was dose-dependently reversed by coincubation with genistein. At genistein concentrations exceeding 6 microM serum-stimulated growth of AGS cancer cells was also inhibited. We conclude that EGF is an important growth factor for AGS gastric cancer cells. Inhibition of the EGFR-associated tyrosine kinase seems to be an effective antiproliferative principle in EGFR-positive human gastric cancer cells.
 ...
PMID:Antiproliferative effect of tyrosine kinase inhibitors in epidermal growth factor-stimulated growth of human gastric cancer cells. 829 23

Genistein, an isoflavone, is a specific inhibitor of tyrosine kinase and topoisomerase II. However, its effect on cell growth is unknown. Therefore, we examined the effects of genistein on cell growth and cell cycle progression and compared its effects with other flavonoids. Genistein inhibited in a dose-dependent manner the growth of HGC-27 cells derived from human gastric cancer. Flow-cytometric analysis showed that genistein almost completely arrested the cell cycle progression at G2-M. This effect was reversible when genistein was removed from the culture medium. In contrast, other flavonoids such as flavone, luteolin, and the structurally similar daidzein arrested the cell cycle at G1. Consistent with the flow-cytometric analysis, microscopic observation showed that genistein did not increase the mitotic index, which supposes that genistein may arrest the cell cycle at G2 or early M. These results suggest that the G2-M arrest by genistein is a unique effect among flavonoids.
 ...
PMID:Genistein arrests cell cycle progression at G2-M. 844 13

The Ron tyrosine kinase receptor shares with the members of its subfamily (Met and Sea) a unique functional feature: the control of cell dissociation, motility, and invasion of extracellular matrices (scattering). The mature Ron protein is a heterodimer of disulfide-linked alpha and beta chains, originated by proteolytic cleavage of a single-chain precursor of 185 kDa. In a human gastric cancer cell line (KATO-III), we found abnormal accumulation of an uncleaved single-chain protein (delta-Ron) of 165 kDa; this molecule is encoded by a transcript differing from the full-length RON mRNA by an in-frame deletion of 49 amino acids in the beta-chain extracellular domain. The deleted transcript originates by an alternatively spliced cassette exon of 147 bp, flanked by two short introns. The delta-Ron tyrosine kinase is constitutively activated by disulfide-linked intracellular oligomerization because it contains an uneven number of cysteine residues. Oligomerization and constitutive tyrosine phosphorylation of the full-size Ron was obtained by site-directed mutagenesis of a single cysteine residue in the region encoded by the cassette exon, mimicking that occurring in the delta-Ron isoform. Inhibition of thiol-mediated intermolecular disulfide bonding prevented delta-Ron oligomerization. The intracellular activation of Ron is followed by acquisition of invasive properties in vitro. These data (i) provide a novel molecular mechanism for posttranscriptional activation of a tyrosine kinase receptor protein and (ii) suggest a role for the Ron receptor in progression toward malignancy.
 ...
PMID:A splicing variant of the RON transcript induces constitutive tyrosine kinase activity and an invasive phenotype. 881 64

Accumulating evidence suggests an important role of interleukin-8 (IL-8) in Helicobacter pylori infection-associated chronic atrophic gastritis and peptic ulcer. We observed in this study that a gastric cancer-derived cell line, MKN45, produced a massive amount of IL-8 upon coculture with live H. pylori but not with killed H. pylori, H. pylori culture supernatants, or live H. pylori separated by a permeable membrane, indicating that IL-8 production requires a direct contact between the cells and live bacteria. Moreover, the tyrosine kinase inhibitor herbimycin but neither a protein kinase C inhibitor (staurosporine) nor a protein kinase A inhibitor (H89) inhibited IL-8 production by MKN45 cells cocultured with live bacteria, suggesting the involvement of a tyrosine kinase(s) in H. pylori-induced IL-8 production. In addition, coculture of H. pylori induced IL-8 mRNA expression in MKN45 cells and an increase in luciferase activity in cells which were transfected with a luciferase expression vector linked with a 5'-flanking region of the IL-8 gene (bp -133 to +44), indicating that the induction of IL-8 production occurred at the transcriptional level. This region contain three cis elements important for induction of IL-8 gene expression: AP-1 (-126 to -120 bp), NF-IL6 (-94 to -81 bp), and NF-kappaB (-80 to -70 bp) binding sites. Mutation of the NF-kappaB binding site abrogated completely the induction of luciferase activity, whereas that of the AP-1 site partially reduced the induction. However, mutation of the NF-IL6 binding site resulted in no decrease in the induction of luciferase activity. Moreover, specific NF-kappaB complexes were detected in the nuclear proteins extracted from MKN45 cells which were infected with H. pylori. Collectively, these results suggest that H. pylori induced the activation of NF-kappaB as well as AP-1, leading to IL-8 gene transcription.
 ...
PMID:Mechanisms involved in Helicobacter pylori-induced interleukin-8 production by a gastric cancer cell line, MKN45. 923 78


1 2 3 4 5 6 7 8 9 10 Next >>