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

It has been advanced that the trefoil factor (TFF) 1 gene is a candidate tumor-suppressor gene and may be involved in the development and/or progression of human gastric cancer. We aimed to clarify the putative role of TFF1 in gastric carcinogenesis. Ninety gastric carcinomas and eight gastric carcinoma-derived cell lines were screened for TFF1 mutations; subsets of the primary tumors and of the cell lines were subjected to loss of heterozygosity (LOH), immunohistochemistry, and promoter methylation analyses. TFF1 mutations were not detected in any of 90 gastric carcinomas. Eight (28%) of 28 informative cases displayed LOH at the TFF1 locus and absence of TFF1 staining by immunohistochemistry. These results indicate a frequent loss of TFF1 expression in gastric carcinomas through a mutation-independent mechanism. Extensive TFF1 promoter methylation was observed in nonexpressing gastric carcinoma-derived cell lines and tissues. Expressing cell lines, as well as normal gastric mucosa, presented little or no methylation of the promoter. Gastric carcinoma DNA presented de novo methylation of the promoter. These results point to the involvement of promoter methylation in the shutting down of TFF1. We conclude that TFF1 point mutations seem to be a rare event in gastric carcinogenesis. The loss of expression of TFF1 in a proportion of gastric carcinomas may be explained by LOH and methylation of the TFF1 promoter region. Our results further support the role of TFF1 inactivation in gastric carcinogenesis, in agreement with the results obtained in the Tff1-knockout mice model.
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PMID:Loss of heterozygosity and promoter methylation, but not mutation, may underlie loss of TFF1 in gastric carcinoma. 1237 66

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