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)

We report the molecular characterization of 8 primary gastric carcinomas, corresponding xenografts, and 2 novel gastric carcinoma cell lines. We compared the tumors and cell lines, with respect to histology, immunohistochemistry, copy number, and hypermethylation of up to 38 genes using methylation-specific multiplex ligation-dependent probe amplification, and TP53 and CDH1 mutation analysis where relevant. The primary tumors and xenografts were histologically comparable and shared expression of 11 of 14 immunohistochemical markers (E-cadherin, beta-catenin, COX-2, p53, p16, TFF1, cyclin E, MLH1, SMAD4, p27, KLK3, CASR, CHFR, and DAPK1). Gains of CASR, DAPK1, and KLK3--not yet described in gastric cancer--were present in the primary tumors, xenografts, and cell lines. The most prominent losses occurred at CDKN2A (p16), CDKN2B (p15), CDKN1B (p27/KIP1), and ATM. Except for ATM, these losses were found only in the cell line or xenograft, suggesting an association with tumor progression. However, examination of p16 and p27 in 174 gastric cancers using tissue microarrays revealed no significant correlation with tumor stage or lymph node status. Further losses and hypermethylation were detected for MLH1, CHFR, RASSF1, and ESR, and were also seen in primary tumors. Loss of CHFR expression correlated significantly with the diffuse phenotype. Interestingly, we found the highest rate of methylation in primary tumors which gave rise to cell lines. In addition, both cell lines harbored mutations in CDH1, encoding E-cadherin. Xenografts and gastric cancer cell lines remain an invaluable research tool in the uncovering of the multistep progression of cancer. The frequent gains, losses, and hypermethylation reported in this study indicate that the involved genes or chromosomal regions may be relevant to gastric carcinogenesis.
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PMID:Molecular analysis of primary gastric cancer, corresponding xenografts, and 2 novel gastric carcinoma cell lines reveals novel alterations in gastric carcinogenesis. 1737 10

Because metastatic cancers are derived from their primary counterparts, their molecular profiles could reasonably be expected to be similar to those of primary cancers. However, this expectation has been proven to be untrue in several human cancers. To explore protein expressional differences in primary and metastatic gastric carcinoma, we evaluated the expressions of 32 tumor-associated proteins in 250 pairs of primary and metastatic gastric carcinoma tissues by immunohistochemistry using tissue array slides. In metastatic gastric carcinomas, the expressions of epidermal growth factor receptor, c-erbB2, and trefoil factor 1(TFF-1) were higher and those of beta-catenin, E-cadherin, fragile histone triad gene (FHIT), glutathione S transferase-pi (GST-pi), kangai 1 (KAI1), and nuclear factor-kappaB (NF-kappaB) were lower than in primary gastric carcinomas. Furthermore, the expressions of beta-catenin, E-cadherin, KAI1, and NF-kappaB were associated with an advanced T and combined stage. In addition, the loss of E-cadherin expression during lymph node metastasis or E-cadherin immunonegativity in metastatic lesions and epidermal growth factor receptor expression in primary gastric carcinomas were independently associated with a poor prognosis by multivariate analysis. In conclusion, the expression of some tumor-associated proteins and their prognostic significance in metastatic gastric carcinomas differ from those in primary tumors. Consequently, analysis of both metastatic gastric carcinomas and their primary counterparts may be required to fully determine the molecular characteristics of node-positive gastric carcinoma.
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PMID:Comparative analysis of protein expressions in primary and metastatic gastric carcinomas. 1883 21

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