Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:2.7.7.48 (transcriptase)
 9,479 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We report on the effect of prolonged hyperglycaemic (11 and 30 mM D-glucose) culture conditions on human mesangial cell matrix metalloproteinases (MMPs), plasminogen activators and their inhibitors. The results indicate that hyperglycaemic conditions modulate the potential proteolytic activity of the enzymes secreted by confluent cultures of these cells. Gelatinase A (MMP-2) activity was always higher in cultures maintained under hyperglycaemic than under normoglycaemic conditions (4 mM D-glucose). In contrast, gelatinase B (MMP-9) activity was decreased under the same conditions. Matrilysin (MMP-7) activity was decreased by up to 100% under hyperglycaemic conditions. Reverse transcriptase-PCR and Western-blotting analyses indicate that in all cases both the transcripts and the protein level were correlated with enzymic activity. One tissue inhibitor of metalloproteinases, TIMP-2, was barely detectable under hyperglycaemic conditions (30 mM D-glucose). In contrast, TIMP-1 increased during the initial 2 weeks of culture in hyperglycaemic conditions and remained elevated to the end of the experiment (4 weeks). Under normoglycaemic conditions TIMP-1 decreased after 2 weeks of culture. Hyperglycaemic conditions also decreased markedly the activity of tissue plasminogen activator (t-PA). This seemed to be due to increased synthesis of its inhibitor, plasminogen activator inhibitor 1, under these conditions rather than to decreased expression of the t-PA enzyme.
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PMID:Modulation of neutral protease expression in human mesangial cells by hyperglycaemic culture. 900 62

Matrix metalloproteinase-7 (MMP-7) is a member of the family of matrix-degrading metalloproteinases that are believed to contribute to the complex process of cancer invasion and metastasis. The secretion level of MMP-7 as assayed by immunoblot analysis was low but distinct in the culture medium of a human colon carcinoma cell line, WIDr, whereas none of the fibroblasts secreted the detectable level of MMP-7. The coculture of WiDr with various human fibroblasts from orthotopic (colon) and ectopic (thyroid, brain, lung, and skin) organs significantly stimulated the secretion of MMP-7 compared with the cultures of individual cells. Reverse transcriptase-polymerase chain reaction analysis and RNA blot analysis suggested that this enhancement occurred at a pretranslational level. The extent of the stimulation was widely varied by the fibroblasts used and was dependent on the cellular ratios and density in the coculture. There may exist a tendency that fibroblasts of orthotopic origin stimulate more extensively than do those of ectopic origin. Moreover, in the coculture of high cell density, normal fibroblasts from the ectopic organs reduced the MMP-7 secretion. The stimulation of MMP-7 secretion may be partially mediated through soluble factor(s); however, direct cell-cell interactions would be required for maximum stimulation. The enhanced MMP-7 secretion was also observed in coculture of colon fibroblasts with other colorectal carcinoma cell lines such as RCM-1 and SW837, which secreted hardly detectable levels of MMP-7 in the individual culture. These results suggest that MMP-7 secretion by colon carcinoma cells is influenced by specific interactions between the carcinoma cells and host fibroblasts.
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PMID:Modulation of matrix metalloproteinase-7 (matrilysin) secretion in coculture of human colon carcinoma cells with fibroblasts from orthotopic and ectopic organs. 922 Apr 95

Matrix metalloproteinase-7 (MMP-7), secreted by cancer cells, has been implicated classically in the basement membrane destruction associated with tumor cell invasion and metastasis. Epidemiological studies have established a correlation between high levels of circulating insulin-like growth factor-1 (IGF-1) and the relative risk of colorectal cancer, which is known to produce MMP-7. We examined the clinicopathological significance of the relative expression of MMP-7, IGF-1, IGF-2 and IGF-1 receptor genes in patients with colorectal cancer, especially with regard to metastasis. We studied surgical specimens of cancer tissue and adjacent normal mucosa obtained from 205 patients with untreated colorectal carcinoma. MMP-7, IGF-1, IGF-2, IGF-1R and beta-actin mRNA in cancer tissue and adjacent normal mucosa were measured by quantitative real-time reverse-transcriptase polymerase chain reaction. MMP-7 and IGF-1R gene expression levels were higher in cancer tissue than in adjacent normal mucosa. In contrast, IGF-1 gene expression was lower in cancer tissue than in adjacent normal mucosa. As for the relationship of gene expression to clinicopathological factors, IGF-1R expression correlated with venous invasion and liver metastasis. IGF-1R gene expression is thus considered a useful predictor of liver metastasis from colorectal cancer.
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PMID:Clinicopathological significance of the gene expression of matrix metalloproteinase-7, insulin-like growth factor-1, insulin-like growth factor-2 and insulin-like growth factor-1 receptor in patients with colorectal cancer: insulin-like growth factor-1 receptor gene expression is a useful predictor of liver metastasis from colorectal cancer. 1863 98

Matrix metalloproteinase-7 (MMP-7), MMP-9, MMP-13, and tissue inhibitor of matrix metalloproteinase-1 (TIMP-1) are considered to have important roles in the invasiveness and outcomes of colorectal cancer (CRC). This study examined the clinicopathological significance of the relative expression of these genes in patients with colorectal cancer, especially as related to liver metastasis. The study analysed surgical specimens of cancer tissue and adjacent normal mucosa obtained from 202 patients with untreated colorectal cancer. MMP-7, MMP-9, MMP-13, TIMP-1, and beta-actin mRNA of cancer tissue and adjacent normal mucosa were measured by quantitative real-time, reverse-transcriptase polymerase chain reaction. Expression levels of MMP-7, MMP-9, MMP-13 and TIMP-1 were higher in cancer tissue than in adjacent normal mucosa. On analysis of the relations between gene expression and clinicopathological factors, MMP-13 expression was found to correlate with liver metastasis. Moreover, MMP-13 expression levels were higher in tumour tissue with liver metastasis than in that without liver metastasis. It is concluded that MMP-13 gene expression is a useful predictor of liver metastasis in patients with CRC.
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PMID:Overexpression of MMP-13 gene in colorectal cancer with liver metastasis. 2068