Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P04155 (pS2)
 1,234 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Gastric carcinoma is the fourth most common cause of cancer death worldwide but its molecular biology is poorly understood. We catalogued the genes expressed in two gastric adenocarcinomas and normal stomach, using serial analysis of gene expression (SAGE), and compared the profiles on-line with other glandular epithelia. Candidates were validated by Northern blotting and immunohistochemistry. A total of 29 480 transcripts, derived from 10 866 genes, were identified. In all, 1% of the genes were differentially expressed (>/=fivefold difference plus P-value </=0.01) between cancers and normal stomach. The most abundant transcripts included ribosomal and mitochondrial proteins, of which most were upregulated in the tumours, as were other widely expressed genes including transcription factors, signalling molecules (serine/threonine protein kinases), thymosin beta 10 and collagenase I. Transcripts abundant in normal stomach were functionally important, including gastrin, immunoglobulin alpha, lysozyme, MUC5, pS2 and pepsinogens, which were among 55 gastric-specific genes. Many transcripts were minimally characterized or new, some cancer-associated genes reflected their intestinal morphology, and some normal gastric genes had previously been considered as pancreatic carcinoma markers. The gastric carcinoma profiles resembled other tumours', supporting the existence of common cancer-associated targets. These data provide a catalogue from which to develop markers for better diagnosis and therapy of gastric carcinoma.
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PMID:Profiling, comparison and validation of gene expression in gastric carcinoma and normal stomach. 1283 51

Through previous large-scale gene expression profiling we identified a transcript that was abundant in normal stomach and down-regulated in gastric cancer. Genes expressed at similar levels included gastrin, MUC5 and pS2, which are important in gastric function. We aimed to characterise this candidate, gastrokine 1 (GKN1), at mRNA, DNA, protein and tissue levels. The gene was studied in human, mouse, rat and cow, and was highly conserved across these species. The mRNA transcripts averaged 750 bp in length. The human, mouse and rat genes all contained six exons spanning 6 kb, and were located on chromosomes 2, 6 and 4 respectively. The full-length translation products were 183-185 amino acids long, reducing to the mature protein of 18 kDa following signal peptide cleavage; these predictions were confirmed by Western blotting. Tagged gastrokine 1 yielded granular cytoplasmic staining with perinuclear accentuation, representing the Golgi apparatus, in keeping with secretion or expression on the extracellular surface. Gene expression in tissues was profiled extensively by Northern blotting, in situ hybridisation and immunohistochemistry. Gastrokine 1 was highly expressed in normal stomach, where it was located in the superficial/foveolar gastric epithelium, but was absent from gastric carcinomas. Outwith the stomach, gastrokine 1 was found only in epithelia showing gastric metaplasia eg Barrett's oesophagus, the ulcer-associated cell lineage and ovarian mucinous neoplasms. In conclusion, we have characterised gastrokine 1, previously known as CA11, AMP-18 or foveolin. Its abundance in, and specificity for, native or metaplastic gastric epithelium, down-regulation in gastric carcinoma and evolutionary conservation suggest that this gene is physiologically important in the stomach. The function of gastrokine 1 is unknown but a role in mucosal protection is postulated.
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PMID:Gastrokine 1 is abundantly and specifically expressed in superficial gastric epithelium, down-regulated in gastric carcinoma, and shows high evolutionary conservation. 1522 38

Invasive pancreatic cancer is thought to develop through a series of noninvasive duct lesions known as pancreatic intraepithelial neoplasia (PanIN). We used cDNA microarrays interrogating 15,000 transcripts to identify 49 genes that were differentially expressed in microdissected early PanIN lesions (PanIN-1B/2) compared with microdissected normal duct epithelium. In this analysis, a cluster of extrapancreatic foregut markers, including pepsinogen C, MUC6, KLF4, and TFF1, was found to be up-regulated in PanIN. Up-regulation of these genes was further validated using combinations of real-time reverse transcription-PCR, in situ hybridization, and immunohistochemistry in a total of 150 early PanIN lesions from 81 patients. Identification of these gastrointestinal transcripts in human PanIN prompted assessment of other foregut markers by both semiquantitative and real-time reverse transcription-PCR, revealing similar up-regulation of Sox-2, Gastrin, HoxA5, GATA4/5/6, Villin and Forkhead 6 (Foxl1). In contrast to frequent expression of multiple gastric epithelial markers, the intestinal markers intestinal fatty acid binding protein, CDX1 and CDX2 were rarely expressed either in PanIN lesions or in invasive pancreatic cancer. Hedgehog pathway activation induced by transfection of immortalized human pancreatic ductal epithelial cells with Gli1 resulted in up-regulation of the majority of foregut markers seen in early PanIN lesions. These data show frequent up-regulation of foregut markers in early PanIN lesions and suggest that PanIN development may involve Hedgehog-mediated conversion to a gastric epithelial differentiation program.
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PMID:Gene expression profiles in pancreatic intraepithelial neoplasia reflect the effects of Hedgehog signaling on pancreatic ductal epithelial cells. 1575 53

H+/K+-ATPase beta-subunit-deficient mice (129/Sv background) display numerous pathologies in the stomach. Expression of the mutation in BALB/cCrSlc mice results in the development of an aberrant 'mucus-rich' cell population. 'Mucus-rich' cells have been described in stomachs of mice with autoimmune gastritis, a disease mediated by CD4+ T cells. Other pathological features of autoimmune gastritis are similar to those in H+/K+ beta-deficient mice and include a mononuclear cell infiltrate in the gastric mucosa, non-functional or absent parietal cells, depletion of zymogenic cells, hypergastrinaemia, and gastric unit hypertrophy caused by immature cell hyperplasia. The present study investigates further the aberrant gastric 'mucus-rich' cell lineage and analyses the mRNA expression of mucus cell products TFF1 and TFF2. 'Mucus-rich' cells stained for both acidic and neutral mucins, and with a TFF2-specific antibody. Stomachs from both models expressed decreased TFF1 mRNA and reciprocally increased TFF2 mRNA. The involvement of gastrin in regulating trefoil mRNA expression was also investigated using gastrin-deficient mice. In contrast to previous findings, gastrin did not positively regulate TFF1 mRNA expression, but there was possible augmentation of TFF2. Additionally, a clear role for inflammation was established involving both polymorphonuclear and mononuclear cells in these models, and a link was found between mucosal hypertrophy and increased interleukin-11 (IL-11) expression.
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PMID:Reciprocal changes in trefoil 1 and 2 expression in stomachs of mice with gastric unit hypertrophy and inflammation. 1598 82

We have investigated how gastric H. pylori infection affects antrum secretory cell types by studying the expression of secretory proteins in antrum epithelium. Antrum biopsy specimens were prospectively collected from 102 individuals (49 H. pylori-infected). Immunohistochemistry was performed for secretory mucins (MUC5AC, MUC5B, MUC6), Trefoil factor family (TFF)-peptides (TFF1, TFF2), endocrine peptides (gastrin, chromogranin A), and proliferating cells (Ki-67). Protein expression was quantified morphometrically. H. pylori infection was significantly correlated to mucosal inflammation and to epithelial atrophy and proliferation. In H. pylori-infected patients the number of proliferating cells increased significantly, and the zone of proliferating cells shifted toward the surface epithelium of the antral glands. Infection was correlated with decreased MUC5AC, TFF1, and TFF2 expression and increased MUC6 and MUC5B expression. Endocrine cells expressing chromagranin A and gastrin shifted toward the surface epithelium of the antral glands in H. pylori-infected patients. H. pylori infection and concomitant inflammation induced increased epithelial proliferation and triggered coordinate deregulation of secretory cell populations in the antrum. In particular, infection led to a coordinated increase in cells expressing MUC6 and MUC5B at the expense of MUC5AC-producing cells.
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PMID:Infection with Helicobacter pylori affects all major secretory cell populations in the human antrum. 1598 58

We previously showed that antral gastric tumors develop in gastrin-deficient (Gas(-/-)) mice. Therefore Gas(-/-) mice were studied sequentially over 12 months to identify molecular mechanisms underlying gastric transformation. Fundic atrophy developed by 9 months in Gas(-/-) mice. Antral mucosal hyperplasia developed coincident with the focal loss of TFF1 and Muc5AC. Microarray analysis of 12 month Gas(-/-) tumors revealed an increase in follistatin, an activin/BMP antagonist. We found that elevated follistatin expression occurred in the proliferative neck zone of hyperplastic antrums, in antral tumors of Gas(-/-) mice, and also in human gastric cancers. Follistatin induced cyclin D1 and the trefoil factors TFF1 and TFF2 in a gastric cancer cell line. We concluded that antral hyperplasia in Gas(-/-) mice involves amplification of mucous cell lineages due to follistatin, suggesting its role in the development of antral gastric tumors.
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PMID:Induction of follistatin precedes gastric transformation in gastrin deficient mice. 1880 92