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)

The expression of the estrogen-regulated breast-cancer-associated pS2 gene was examined in 75 stomach resections taken from 45 patients. The 600-base pS2 mRNA was found in all of the 47 non-neoplastic samples at varying levels: in the histologically normal group we observed a Poisson-type distribution, whereas 79% of the tissues exhibiting dysplastic features expressed high levels of transcript. Tumour samples expressed relatively lower pS2 mRNA, with only 18% having high levels and 43% with no detectable expression. These differences were not correlated to tumour grading, stage or site. No amplification or rearrangement of the pS2 gene was found. Immunohistochemical analysis of formalin-fixed paraffin sections, using a polyclonal antibody against pS2 protein, showed specific staining of both cytoplasm and membrane of epithelial cells in the neck region of antral and body glands as well as in luminal secretions. Immunoreactivity was observed in the sub-nuclear region of foveolar cells, with specialized gland and goblet cells in atrophic gastritis being negative. Heterogeneous but strong focal cytoplasmic staining was seen in tumour cells as well as in dysplastic epithelium. Two gastric cell lines, KATO III and MKN-45, derived from poorly differentiated adenocarcinomas also expressed pS2, whereas 3 other lines from well differentiated parental tumours did not. Genomic analysis revealed a BamHI polymorphism in Kato III cells and in the non-expressing MKN-28 cells. Immunostaining to pS2 protein was also demonstrated in the cytoplasm of KATO III cells, but neither these nor any of 30 tissues examined showed any positivity with a monoclonal antibody (MAb) to estrogen receptor. Our results suggest that pS2 is normally expressed in human stomach, possibly in association with secretory activity, and becomes down-regulated during malignancy.
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PMID:Expression of the pS2 gene in normal, benign and neoplastic human stomach. 258 60

The aim of this study was to evaluate the pattern of pS2 protein expression in premalignant and malignant lesions of gastric epithelium. We analysed, by immunohistochemistry, the pS2 expression in six samples of normal gastric mucosa, 18 cases of chronic atrophic gastritis with intestinal metaplasia (IM), 10 hyperplastic polyps, 11 adenomatous polyps and 50 gastric carcinomas, together with the respective samples of adjacent non-neoplastic mucosa. pS2 is expressed throughout foveolar and superficial epithelium of normal gastric mucosa and this pattern is retained in chronic atrophic gastritis out of IM lesions. pS2 expression is confined to goblet cells in complete IM and occurs both in goblet and columnar cells in incomplete IM. Hyperplastic polyps displayed significantly higher pS2 expression than adenomatous polyps. In gastric carcinomas, pS2 expression was observed in 66.0% of cases, being significantly higher in diffuse (88.9%) than intestinal type carcinomas (53.6%). A subset of carcinomas of the latter group displayed pS2 immunoreactivity in a high percentage of cells with a pattern similar to that of hyperplastic polyps. Our results demonstrate there are major changes in pS2 expression, which can be used as a marker of gastric-type differentiation during the process of gastric carcinogenesis, and support the existence of at least two pathways of malignant transformation of gastric mucosa: one via intestinal metaplasia and adenomatous dysplasia, leading to glandular carcinomas with intestinal-type differentiation, the other via hyperplastic changes or de novo changes, leading to diffuse carcinomas and to a subset of glandular carcinomas displaying gastric-type differentiation.
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PMID:Pattern of pS2 protein expression in premalignant and malignant lesions of gastric mucosa. 881 6

The trefoil peptides spasmolytic polypeptide (SP), intestinal trefoil factor (ITF), and pS2 show lineage-specific expression in the normal gut and are strongly induced after mucosal injury. We assessed the relationship between this induction and the development of the regenerative epithelial lineage over time in the rat stomach and verified these observations in the metaplastic and dysplastic human stomach. Antral or colonic ulcers were induced in Wistar rats by application of serosal acetic acid and tissues harvested 2 hours to 125 days later. Human endoscopic biopsies or gastric resection specimens were also assessed. Tissues were examined by radioimmunoassay, immunoblotting, or immunohistochemistry for ITF, SP, and transforming growth factor alpha (rat) or ITF and pS2 (human) expression. ITF and SP mRNA in antral ulcer margins was localized by in situ hybridization. ITF and SP peptide expression rose steadily in ulcer margins after 4 days, with the rise in ITF being more pronounced. By 40 days, several hundred-fold elevations in ITF levels were present, with a field effect in uninvolved mucosa. Hyperproliferative, elongated glands of undifferentiated cells expressing abundant trefoil peptides and acid sulfomucins were present after day 12 and persisted after ulcer healing. ITF mRNA was aberrantly expressed in basal and mid-regions of these regenerative glands. In contrast, transforming growth factor alpha peptide expression rose promptly after injury then fell to baseline levels with healing. Seven months after injury, gastric atrophy, intestinal metaplasia, and severe dysplasia with conserved ITF expression were seen. ITF was also induced in human intestinal metaplasia and conserved in all gastric cancers, whereas expression of the gastric peptide pS2 was progressively reduced in the progression from metaplasia to dysplasia. Persistent, selective overexpression of ITF, possibly acting in an autocrine fashion, is a feature of regeneration after antral ulceration, and may provide insight into the nature of metaplastic phenotypes arising from chronic gastric injury. The loss of pS2 expression in metaplasia and cancer supports a role for this protein in gastric tumor suppression.
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PMID:Augmented intestinal trefoil factor (TFF3) and loss of pS2 (TFF1) expression precedes metaplastic differentiation of gastric epithelium. 1131 Aug 32

TFF1/pS2, TFF2/SP and TFF3/ITF are soluble peptides with trefoil domain(s) and C-terminal dimerization domain, which are conserved among human, cow, mouse and rat. TFF1 mRNA is expressed in stomach (mucous cells in fundus and antrum), TFF2 mRNA in stomach (mucous neck cells in fundus and basal cells in antral and pyloric glands) and duodenum (Brunner's gland), TFF3 mRNA in small intestine and large intestine (goblet cells). Expression of TFF1, TFF2 and TFF3 mRNAs are differentially regulated by FGF2/bFGF, FGF7/KGF, estrogen, aspirin, arachidonic acid, X-ray irradiation, and hydrogen peroxide. Gastric cancer is classified into the intestinal type and the diffuse type. TFF mRNAs are preferentially expressed in diffuse-type gastric cancer cells. Custom-made microarray (TFF mRNAs) and ELISA (TFF proteins) might be applicable for screening methods of peritoneal and bone marrow dissemination from diffuse-type gastric cancer. TFF1 and TFF2 mRNAs are frequently down-regulated in intestinal-type gastric cancer. TFF1 gene, inactivated by deletion, missense mutation and promoter hypermethylation, is a tumor suppressor gene implicated in gastric cancer. TFF2 is a candidate tumor suppressor gene; however, genetic and epigenetic alterations of TFF2 gene in human gastric cancer remain unclear. TFF1, TFF2 and TFF3 play key roles in mucosal protection through mucous-barrier formation, and also in mucosal repair through promotion of restitution after injury. Patients with chronic atrophic gastritis and those with ulcerative colitis are at risk of gastric cancer and colorectal cancer, respectively. TFF1, TFF2 and TFF3 proteins might be applicable for chemoprevention of gastrointestinal cancer associated with chronic persistent inflammation.
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PMID:Trefoil factors and human gastric cancer (review). 1279 1

Sporadic fundic gland polyps (FGP) are the most common type of gastric polyps and their pathogenesis is still unclear, although a beta-catenin gene mutation has been described. They are regarded as benign lesions but low-grade dysplasia has been observed, arising more debate on their potential progression to a malignant phenotype. We investigated in FGP the role of factors involved in cell integrity, proliferation, and intercellular adhesion: trefoil peptides (TFF1, TFF2), MIB1, E-cadherin, and beta-catenin. We selected randomly 24 patients with FGP, 24 with normal gastric mucosa and 12 with atrophic gastritis with diffuse intestinal metaplasia (IM-gastritis), all Helicobacter pylori negative. The expression of all factors was examined by immunohistochemistry. In polyps and normal mucosa, TFF1 is expressed only in foveolar compartment whereas in IM-gastritis the signal is reduced in all the compartments. TFF2 is expressed in polyps and normal mucosa, in proliferative and basal compartment, whereas in IM-gastritis the expression is reduced or absent. E-cadherin is expressed in the entire zone: with a medium signal in normal mucosa and polyps, and weaker in IM-gastritis. The beta-catenin's signal in normal mucosa and polyps is moderate-to-intense in proliferative and basal compartments, whereas in IM-gastritis signal is significantly reduced in all the compartments. MIB1 in normal mucosa and polyps is expressed only in proliferative compartment, whereas its expression is stronger in IM-gastritis and involves also basal compartment. In conclusion all the factors considered were normally expressed in FGP and this, especially considered against the findings in IM-gastritis, supports the benign nature of FGP.
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PMID:Trefoil peptides, E-cadherin, and beta-catenin expression in sporadic fundic gland polyps: further evidence toward the benign nature of these lesions. 1944 76

Helicobacter pylori infection increases age-related diverse overmethylation in gene-control regions, which increases the risk of gastric cancer. The H. pylori-associated overmethylation changes subsequently disappear when gastric atrophy and cancer develop. To identify cancer-risk epigenotypes, we traced dynamic methylation changes in the background mucosa of the stomach depending on the extent of gastric atrophy. Paired biopsy specimens were obtained from the noncancerous antrum and body mucosa of 102 patients with cancer and 114 H. pylori-positive and 112 H. pylori-negative controls. The grade of gastric atrophy was evaluated using the endoscopic atrophic border score. The methylation-variable sites at the CpG-island margins and near the transcriptional start sites lacking CpG islands were semiquantitatively analyzed by radioisotope-labeling methylation-specific PCR. We selected eight housekeeping genes adjacent to Alu (CDH1, ARRDC4, PPARG, and TRAPPC2L) or LTR retroelements (MMP2, CDKN2A, RUNX2, and RUNX3) and eight stomach-specific genes (TFF2, PGC, ATP4B, TFF1, TFF3, GHRL, PGA, and ATP4A). Analysis of age-related methylation in the H. pylori-positive controls revealed slow overmethylation in the body and in the LTR-adjacent genes. A high-frequency overmethylation defined based on the slowly overmethylated genes was frequently observed in the body of patients with gastric cancer with open-type atrophy (OR, 12.7; 95% confidence interval, 3.2-49.8). The rapidly changing methylation of Alu-adjacent genes was barely increased in the antrum of patients with gastric cancer. Among diverse methylation changes associated with H. pylori infection, an increase in slowly changing methylation could serve as a cancer-risk marker.
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PMID:Slow overmethylation of housekeeping genes in the body mucosa is associated with the risk for gastric cancer. 2465 29