Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0178874 (tumor progression)
 40,807 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A cDNA encoding a new member of the membrane-type (MT) matrix metalloproteinase (MMP) family has been identified and cloned from a human brain cDNA library. The isolated cDNA encodes a polypeptide of 645 amino acids that displays a similar domain organization as other MMPs, including a predomain with the activation locus, a zinc-binding site, and a hemopexin domain. The deduced amino acid sequence contains a COOH-terminal extension, rich in hydrophobic residues and similar in size to the equivalent domains identified in MT-MMPs. Immunofluorescence and Western blot analysis of COS-7 cells transfected with the isolated cDNA revealed that the encoded protein is localized in the plasma membrane. On the basis of these features, this novel human MMP has been called MT5-MMP because it represents the fifth member of the MT-MMP subfamily of MMPs. Fluorescent in situ hybridization experiments showed that the human MT5-MMP gene (MMP-24) maps to 20q11.2, a region frequently amplified in tumors from diverse sources. Northern blot analysis demonstrated that MT5-MMP is predominantly expressed in brain, kidney, pancreas, and lung. In addition, MT5-MMP transcripts were detected at high levels compared to normal brain tissue in a series of brain tumors, including astrocytomas and glioblastomas. The catalytic domain of MT5-MMP, produced in Escherichia coli as a fusion protein with glutathione S-transferase, exhibits a potent proteolytic activity against progelatinase A, leading to the generation of the Mr 62,000 active form of this enzyme. These data suggest that MT5-MMP may contribute to the activation of progelatinase A in tumor tissues, in which it is overexpressed, thereby facilitating tumor progression.
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PMID:Identification and characterization of human MT5-MMP, a new membrane-bound activator of progelatinase a overexpressed in brain tumors. 1036 75

Leukolysin/membrane-type 6 matrix metalloproteinase (leukolysin/MT6-MMP), a glycosylphosphatidylinositol-anchored neutrophil matrix metalloproteinase, is also abnormally expressed in brain cancer tissues. Yet, little is known about its role in cancer progression. Here we show that MT6-MMP is capable of activating proMMP-2, an enzyme implicated in tumor invasion and metastasis. Although MT6-MMP is only 10% as active as MT5-MMP in mediating proMMP-2 activation, it generates a higher ratio of mature/intermediate forms of MMP-2 than MT5-MMP. Consistently, purified CAT of MT6-MMP converts proMMP-2 into mostly the mature form. Using the catalytically inactive mutant MMP-2EA (the E404A mutant of proMMP-2), which cannot autocatalytically mature from the intermediate form into the mature one, we show that MT6-MMP cleaves not only the known MT-MMP-processing site at Asn(66)-Leu but also the previously unsuspected Asn(109)-Tyr to yield a fully mature molecule. Despite their difference in mediating proMMP-2 activation in transfected cells, the CAT of MT6-MMP appears to be as efficient as that of MT5-MMP in cleaving proMMP-2EA in buffer, suggesting that its CAT is a strong proMMP-2 activator. Indeed, the CAT of MT6-MMP can partially substitute the CAT of prototypical MT1-MMP in mediating proMMP-2 activation. Taken these facts together, we conclude that MT6-MMP may participate in tumor invasion and metastasis by directly converting proMMP-2 into active form.
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PMID:Direct activation of pro-matrix metalloproteinase-2 by leukolysin/membrane-type 6 matrix metalloproteinase/matrix metalloproteinase 25 at the asn(109)-Tyr bond. 1458 71

Zinc-finger protein 217 (ZNF217), which is overexpressed during cancer progression, can promote tumor cell immortalization. To examine the function of ZNF217, a global expression profile was carried out using Affymetrix Gene Chip analysis with HG-U133 plus 2.0 arrays in the ovarian cancer cell line HO-8910 after silencing of the ZNF217 gene. The results were analyzed using the Gene Ontology program to investigate the functional network affected by ZNF217 in ovarian cancer cells. Changes in the mRNA expression of the affected genes were confirmed by real-time reverse transcriptase-polymerase chain reaction (RT-PCR). The results showed that the ZNF217 gene is a key regulator of ovarian cancer, as the silencing of ZNF217 resulted in significant down-regulation by at least 8-fold of 164 genes in the HO-8910 cell line compared to non-silenced control cells. Among these down-regulated genes were ALOX15, CD1D, FXYD3, GAS6, KRT4, LIN7B, MMP-24, PDZK1, PEX6, PRSS8, SLC2A9, STRN and WFDC2. Down-regulation was confirmed by real-time RT-PCR after the silencing of ZNF217 (p<0.05). The results suggest that ZNF217 plays a central role in malignant processes in ovarian cancer.
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PMID:Microarray analysis of gene expression in the ovarian cancer cell line HO-8910 with silencing of the ZNF217 gene. 2147 12