Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.4.24.35 (matrix metalloproteinase 9)
 2,207 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We previously reported that connexin (Cx) 26 expression is involved in negative growth control of HepG2 cells established from a human hepatoma. We also found that induction of E-cadherin and subsequent formation of a cell adhesion complex were induced in HepG2 cells by Cx 26 expression. To examine the exact role of Cx 26-induced E-cadherin junctions in regulating appearance of malignant phenotypes of HepG2 cells, we expressed a Cx 26 antisense oligodeoxynucleotide (AS-ODN) in an established HepG2 cell clone that has stable expression of Cx 26 genes. We investigated changes in the expression of E-cadherin, the localization of beta-catenin, and some malignant phenotypes of HepG2 clone after the suppression of Cx 26 expression by AS-ODN treatment. The AS-ODN treatment prevented the expression of Cx 26 and E-cadherin, and the localization of beta-catenin was changed from cytoplasmic membrane to the cytoplasm. In parallel, a morphological change from a monolayer of polygonal cells to multilayered colonies was induced by the treatment, indicating a change of a malignant phenotype of HepG2 cells. The activity of matrix metalloproteinase 9 (MMP-9) was elevated by the AS-ODN treatment. A concomitant increase in invasiveness of the Cx 26-expressing cells by the treatment was also observed in an in vitro assay with Matrigel matrix. These results suggest that the induction of E-cadherin and formation of the cell adhesion complex by Cx 26 expression contribute to the reversal of some malignant phenotypes of HepG2 cells. Furthermore, the Cx 26-dependent expression of E-cadherin leads to reduction of the invasiveness of the cells through suppression of MMP-9 activity.
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PMID:Regulation of cellular invasion and matrix metalloproteinase activity in HepG2 cell by connexin 26 transfection. 1142 87

Wilms' tumour is a pediatric neoplasm exhibiting histologic features of developing kidney. Although the majority of Wilms' tumour patients are treated effectively, approximately 15% develop metastases and of these, 30% succumb to their disease. The biologic factors governing Wilms' tumour metastasis are largely unknown. Attempts at deriving representative Wilms' tumour cell lines, which could facilitate functional studies, have only been partially successful thus far. We now report on derivation and characterization of a Wilms' tumour cell line, WiT 49, from a first-generation xenograft of a human Wilms' tumour lung metastasis. WiT 49 recapitulates the phenotype of the parent tumours (primary and lung metastasis) and expresses normal WT1, overexpresses IGFII and carries a frequently identified p53 mutation. We recently reported overexpression of hepatocyte growth factor(HGF) and its receptor met in a series of Wilms' tumours with higher levels in homotypic metastatic cases. We therefore examined WiT 49 for expression of HGF/met and for met signaling targets associated with cell adhesion and cytoplasmic mediators of transcription using Western blot, co-immunoprecipitation, immunofluorescence labeling and zymography. Our results show co-expression of HGF and met protein, absence of E-cadherin, high levels of beta-catenin co-immunolocalized to met at the cell membrane and moderate levels of gamma-catenin and ezrin protein expression. After cell fractionation, beta-catenin was detected in the cytoplasm and nuclei of WiT 49 with relatively higher levels in the cytoplasm as compared to nuclei. Examination of MMP expression in WiT 49 showed constitutive activation of MMP 9 and latent MMP 2 supporting possible beta-catenin-mediated transcriptional activation. The WiT 49 cell line responded to recombinant human HGF by an increase in the expression of the met receptor, recruitment of the Gab-1 adapter protein to met and release of bound beta-catenin from met. Our studies therefore establish WiT 49 as a representative Wilms' tumour cell line derived from a lung metastasis that co-expresses HGF/met and shows absence of the cadherin-catenin complex supporting a role for these factors in regulation of the invasive and metastatic phenotype in Wilms' tumour.
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PMID:Derivation and characterization of a Wilms' tumour cell line, WiT 49. 1450 35

The role of expression of markers (beta-catenin, matrix metalloproteinase 9, collagen IV, and laminin) in primary colorectal adenocarcinomas and their metastases in the liver and lymph nodes of patients with colorectal cancer was studied. High level of matrix metalloproteinase 9 expression in zones of invasive growth of colorectal cancer was associated with high accumulation of beta-catenin in cancer cell nuclei in the peripheral zones of 30% studied tumors. The presence of nuclear beta-catenin and high content of matrix metalloproteinase 9 in the tumor were associated with abnormal accumulation of laminin in the cytoplasm and with the absence of basal membranes containing collagen IV. These changes were characteristic of colorectal cancer with high invasive metastatic potential. It was found that beta-catenin, matrix metalloproteinase 9, laminin, and collagen IV were important markers for prediction of the clinical course of colorectal cancer. The expression of proteins associated with risk of metastases in the liver was coordinated and most pronounced in zone of invasive front-line of tumors.
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PMID:Clinical significance of levels of molecular biological markers in zones of invasive front-line of colorectal cancer. 1952 5

Extracellular matrix remodeling is necessary for ectopic endometrium implantation. Many studies have shown an increased expression of matrix metalloproteinase 9 (MMP9) in the ectopic endometrium of endometriosis. However, the signaling pathways and cellular effects related to this process remain incompletely elucidated. The objective of our study was to investigate the association between MMP9 and the Wnt signaling pathway under the regulation of 17beta-estradiol (E2) in endometrial stromal cells. We found that MMP9 was elevated in tissues from women with endometriosis compared with normal women. Furthermore, MMP9 and beta-catenin increased concurrently in a time- and dose-dependent manner after E2 treatment. To clarify the relationship between MMP9 and beta-catenin, we performed luciferase promoter reporter and chromatin immunoprecipitation assays. A beta-catenin/TCF3/LEF1 complex bound to a specific site on the MMP9 promoter that promoted MMP9 gene and protein expression. The promotion of MMP9 by the Wnt signaling pathway under the regulation of E2 may contribute to the pathophysiology of this disease.
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PMID:Intracellular Wnt/Beta-Catenin Signaling Underlying 17beta-Estradiol-Induced Matrix Metalloproteinase 9 Expression in Human Endometriosis. 2688 69