Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P43146 (tumour suppressor)
 5,935 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

WFDC1 is a recently isolated human gene identified as a tumour suppressor gene candidate. It is not known whether alterations in this gene are associated with human cancers. The WFDC1 gene maps in human chromosome 16q24, an area of frequent loss of heterozygosity (LOH) in several tumour types, in particular in hepatocellular carcinoma (HCC). We investigated its role in 46 European HCC by means of the detection of LOH at the WFDC1 locus. We describe here an assay for the detection of loss of heterozygosity at this locus using two dinucleotide repeat polymorphisms identified in WFDC1 introns, with a combined informativity of 86%. LOH was observed in 4/40 informative HCC samples. We further investigated the role of WFDC1 as a tumour suppressor gene candidate in five hepatocellular cell lines and in tumours exhibiting LOH by means of mutation, promoter methylation and gene expression analysis. In HCC samples showing LOH, no mutation of the remaining allele was observed. No significant up or down gene expression was observed in tumour samples comparatively to normal liver and gene expression did not seem related to promoter methylation. These results suggest a minor role, if any, of WFDC1 in hepatocarcinogenesis. However, this approach might be useful for investigating the role of this candidate tumour suppressor gene in other tumour types.
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PMID:Analysis of alterations of WFDC1, a new putative tumour suppressor gene, in hepatocellular carcinoma. 1203 31

The present evaluates the key features of the WFDC1 [WAP (whey acidic protein) four disulfide core 1] gene that encodes ps20 (20 kDa prostate stromal protein), a member of the WAP family. ps20 was first characterized as a growth inhibitory activity that was secreted by fetal urogenital sinus mesenchymal cells. Purified ps20 exhibited several activities that centre on cell adhesion, migration and proliferation. The WFDC1 gene was cloned, contained seven exons, and was mapped to chromosome 16q24, suggesting that it may function as a tumour suppressor; however, direct evidence of this has not emerged. In vivo, ps20 stimulated angiogenesis, although expression of WFDC1/ps20 was down-regulated in the reactive stroma tumour microenvironment in prostate cancer. WFDC1 expression is differential in other cancers and inflammatory conditions. Recent studies point to a role in viral infectivity. Although mechanisms of action are not fully understood, WFDC1/ps20 is emerging as a secreted matricellular protein that probably affects response to micro-organisms and tissue repair homoeostasis.
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PMID:The WFDC1 gene: role in wound response and tissue homoeostasis. 2193 33