Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

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Query: EC:3.4.24.35 (matrix metalloproteinase 9)
2,207 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The in vitro invasive ability, the expression of cell adhesion molecule E-cadherin, activity of matrix metalloproteinase (MMP) and K-ras point mutation were investigated in eight human endometrial carcinoma cell lines. 1) In vitro invasive abilities of endometrial carcinoma cell lines depend on the degree of cell differentiation and the origin of cell lines. A poorly-differentiated carcinoma cell line (NUE-1) and a cell line derived from metastatic lymph node (SNG-M) were more invasive than moderately-(HEC-1A, HEC-1BE) and well-differentiated (HEC-6, Ishikawa) cell lines. 2) Immunohistochemically, less or non-invasive cell lines expressed E-cadherin strongly, whereas a highly invasive cell line (NUE-1) expressed E-cadherin weakly. 3) When cultured on Matrigel-coated dishes, the tumor cells derived from moderately- and well-differentiated carcinoma aggregated with each other and did not invade Matrigel in the invasion assay. The aggregated cells expressed E-cadherin more strongly when cultured on Matrigel. 4) 72-kD gelatinase (MMP-2) was secreted in serum-free conditioned medium of all cell lines. In an invasive cell line (NUE-1,SNG-M), the activity of MMP-2 was stronger than in other cell lines. And the activity of 92-kDa gelatinase (MMP-9) was detected in most invasive cell line (NUE-1). 5) Point mutation of K-ras codon 12 was detected in four of eight (50%) cell lines by the PCR-RFLP method. The changes in the DNA sequence were identified, but K-ras point mutation was not correlated with in vitro invasiveness of the tumor cells.
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PMID:[The factors involved in invasive ability of endometrial carcinoma cells]. 804 Jun 23

We examined the expression of E-cadherin and collagenase type IV in formalin-fixed, paraffin-embedded specimens of human gastric carcinoma by an in situ mRNA hybridization (ISH) technique. The ISH technique revealed intertumoral heterogeneity for expression of E-cadherin and collagenase among 12 cases of early gastric cancer and 13 cases of advanced gastric cancer. In the majority of the tumors, we found an inverse relationship between the reactivities of E-cadherin and collagenase type IV. Specifically, E-cadherin was expressed at higher levels in the center of the neoplasms than in their periphery, whereas collagenase type IV was expressed at a higher level in the periphery (invasive edge) than in the center. Advanced gastric cancers with high levels of expression for collagenase type IV in the periphery had a higher incidence of distant lymph node metastasis than those with low expression. The data show an inverse relationship between E-cadherin (involved in cell-to-cell adhesion) and collagenase type IV (involved in invasion) in different zones of human gastric carcinoma and suggest that the relative expression of these independent genes may be involved in local invasion and metastasis.
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PMID:Intratumoral heterogeneity and inverse correlation between expression of E-cadherin and collagenase type IV in human gastric carcinomas. 864 46

During the process of invasion, tumor cells must detach from the primary neoplasm and degrade host stroma. E-cadherin is responsible for the cell-cell adhesion and collagenase IV is the one of the matrix metalloproteinases. We determined whether the levels of mRNA for E-cadherin and collagenase IV were differently expressed within 12 cases of early and 13 cases of advanced gastric cancers using a rapid calorimetric in situ hybridization assay for mRNA. In 6 of 12 early cancers, we found a decreased expression of E-cadherin mRNA in the invasion edge compared to the main tumor. In advanced gastric cancers, 3 out of 13 cancers also exhibited this finding. Higher expression of the collagenase IV at the invasion edge of the tumor compared to the main tumor was observed in half of the early and advanced gastric cancer cases. Inverse expression levels of E-cadherin and collagenase IV mRNA were observed in 6 of 12 early cancers. However, only one of 13 advanced cancer cases expressed the same finding.
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PMID:[Comparative study of mRNA expression of E-cadherin and collagenase IV in early and advanced cancers]. 867 57

We determined whether the upregulation of several metastasis-related genes in human colon carcinoma (HCC) cells implanted into the cecal wall of nude mice precedes HCC invasion of the muscle layer and subserosa and, ultimately, distant metastasis. HCC KM12SM cells were implanted into the subcutis (ectopic) or cecal wall (orthotopic). At weekly intervals for up to 6 weeks, cecectomy and resection of SC tumors were performed on different groups of mice. Survival and metastasis were assessed at 13 weeks. During the first 2 weeks after orthotopic implantation, the HCC cells grew progressively in the mucosa and submucosal layers of the cecum. By the third week, the cells invaded the muscularis propria and then the serosa. All mice undergoing cecectomy at weeks 1 and 2 were cured, whereas those undergoing cecectomy at later weeks were not. In situ hybridization analysis for expression of several metastasis-related genes-epidermal growth factor receptor (EGF-R), basic fibroblast growth factor (bFGF), collagenase type IV, and E-cadherin-revealed that the expression level of EGF-R, bFGF, and collagenase type IV in the early cecal tumors was low but increased just before invasion of the muscularis propria. At all times, the level of gene expression in the cecal tumors was higher than in the SC tumors. In contrast, the expression level of E-cadherin remained constant and did not differ between tumors in ectopic or orthotopic organs. The data suggest that the upregulation of some metastasis-related genes precedes tumor cell invasion and production of metastasis.
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PMID:Progressive upregulation of metastasis-related genes in human colon cancer cells implanted into the cecum of nude mice. 886 66

We examined the expression level of several genes that regulate different steps of metastasis in formalin-fixed, paraffin-embedded archival specimens of primary human colon carcinomas from patients with at least 5 years of follow-up. The expression of epidermal growth factor receptor, basic fibroblast growth factor, type IV collagenase, E-cadherin, and multidrug resistance (mdr-1) was examined by a colorimetric in situ mRNA hybridization technique concentrating on reactivity at the periphery of the neoplasms. The in situ hybridization technique revealed inter- and intratumor heterogeneity for expression of the metastasis-related genes. The expression of basic fibroblast growth factor, collagenase type IV, epidermal growth factor receptor, and mdr-1 mRNA was higher in Dukes's stage D than in Dukes' stage B tumors. Among the 22 Dukes' stage B neoplasms, 5 specimens exhibited a high expression level of epidermal growth factor receptor, basic fibroblast growth factor, and collagenase type IV. Clinical outcome data (5-year follow-up) revealed that all 5 patients with Dukes' stage B tumors developed distant metastasis (recurrent disease), whereas the other 17 patients with Dukes' stage B tumors expressing low levels of the metastasis-related genes were disease-free. Multivariate analysis identified high levels of expression of collagenase type IV and low levels of expression of E-cadherin as independent factors significantly associated with metastasis or recurrent disease. More specifically, metastatic or recurrent disease was associated with a high ratio (> 1.35) of expression of collagenase type IV to E-cadherin (specificity of 95%). Collectively, the data show that multiparametric in situ hybridization analysis for several metastasis-related genes may predict the metastatic potential, and hence the clinical outcome, of individual lymph-node-negative human colon cancers.
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PMID:Multiparametric in situ mRNA hybridization analysis to predict disease recurrence in patients with colon carcinoma. 890 44

Diploid mouse embryos containing only maternal DNA (parthenotes) fail, in part, because the inner cell mass does not induce the trophoblast to grow. In this study, we asked whether any of the defects in parthenotes may arise from alterations in trophoblast function. We examined the expression of genes important for normal trophoblast function and found several trophoblast genes that were expressed at normal levels in the primary trophoblast cells of parthenotes: E-cadherin, a cell adhesion molecule, was expressed normally in both the ICM and trophectoderm of parthenogenetic blastocysts and blastocyst outgrowths; the gene for Hxt, a basic helix-loop-helix factor that regulates trophoblast development, was expressed in both zygotic and parthenogenetic giant cells; placental lactogen-1, a hormone that is normally secreted by trophoblast giant cells, was expressed in most of both parthenogenetic and normal trophoblast cells; and the 92 kDa matrix metalloproteinase, gelatinase B, also known as MMP-9, was secreted at equivalent levels by both zygotic and parthenogenetic blastocyst outgrowths. However, once the outgrowths had developed, a subpopulation of trophoblast cells in parthenogenetic embryos had decreased DNA replication and significantly fewer nucleoli per nucleus than did zygotic embryos. Moreover, the parthenogenetic trophoblast cells growing out from blastocysts had a decreased viability in culture. These data suggest that, although parthenogenetic embryos are able to initiate primary trophoblast differentiation, the stability and continued differentiation of trophoblast giant cells may be abnormal. Our data support the hypothesis that the deficiency of secondary trophoblast giant cells may contribute to the decline of parthenogenetic embryos and suggest that the factors controlling this subset of trophoblast are distinct from those for primary trophoblast.
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PMID:Functional analysis of trophoblast giant cells in parthenogenetic mouse embryos. 909 6

The purpose of this study was to determine whether the expression level of several metastasis-regulating genes correlates with the metastatic potential of human prostate cancer cells implanted into the prostate of nude mice. The steady-state mRNA expression levels for epidermal growth factor receptor (EGFR; growth), basic fibroblast growth factor (bFGF) and interleukin (IL)-8 (angiogenesis), 72-kd and 92-kd type IV collagenase (invasion), E-cadherin (adhesion), and multidrug resistance (mdr-1; drug resistance) were measured by Northern blot and colorimetric in situ hybridization techniques in human PC-3M cells and selected cell variants with different metastatic potentials. Highly metastatic cells growing in culture constitutively and uniformly expressed higher levels of bFGF, IL-8, type IV collagenase, and mdr-1 mRNA transcripts than parental PC-3M cells or low metastatic cells, which displayed a heterogeneous pattern of gene expression. Human prostate cancer cells implanted in nude mice at an ectopic site (subcutaneous) expressed lower levels of EGFR, mdr-1, bFGF, IL-8, and collagenase type IV than those implanted in an orthotopic site (prostate), indicating that the expression of these genes was dependent on the organ environment. Highly metastatic cells growing in the prostate expressed higher levels of EGFR, bFGF, type IV collagenase, and mdr-1 mRNA than low metastatic parental cells in the same site. These data demonstrate a direct correlation between the expression of several metastasis-related genes and the metastatic potential of human prostate cancer cells in nude mice and suggest that multiparametric in situ hybridization analyses can be used to identify the metastatic potential of individual patients' prostate cancers.
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PMID:Correlation of metastasis-related gene expression with metastatic potential in human prostate carcinoma cells implanted in nude mice using an in situ messenger RNA hybridization technique. 913 84

It was determined whether the expression level of several genes that regulate different steps of metastasis in formalin-fixed paraffin-embedded archival specimens of human gastric cancers correlated with disease recurrence and metastasis. The steady-state mRNA expression level for epidermal growth factor receptor (EGF-R), basic fibroblast growth factor (bFGF), E-cadherin, type IV collagenase and multidrug resistance (MDR-1) were examined by a colorimetric in situ hybridisation (ISH) technique, concentrating on reactivity at the periphery of the lesions. All patients were operated on for cure. 15 cases were disease-free and 10 had disease recurrence by 4.5 years after resection of the primary tumours. The expression of EGF-R and bFGF type IV collagenase was higher and expression of E-cadherin was lower in the disease-recurrence cases than in the disease-free cases. The ratio between the expression level of collagenase type IV and E-cadherin at the periphery of the surgical specimens differed significantly between the disease-free cases and the recurrent-metastatic cases. These data show that multiparametric ISH analysis for several metastasis-related genes may allow prediction of disease recurrence of gastric cancer.
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PMID:Expression of metastasis-related genes in surgical specimens of human gastric cancer can predict disease recurrence. 971 9

Proteins secreted by epidermal keratinocytes are known to engage in functions other than those directly associated with barrier formation. We have used a previously published culture model to collect proteins secreted by adult human epidermal keratinocytes. Electrophoresis and microsequencing allowed us to identify 20 proteins. The list of proteins includes those known to be produced by keratinocytes (beta-2 microglobulin, betaIG-H3, calgranulin A, cathepsin B and D, E-cadherin, gelatinase B, gelsolin, interstitial collagenase, laminin B2t, plasminogen activator inhibitor-1, protein 14-3-3epsilon, SCC antigen, stratifin, and translationally controlled tumor protein) as well as those not previously known to be secreted by keratinocytes (epididymis secretory protein, maspin, and anti-neoplastic urinary protein). In addition, two proteins were identified that are not known to be secreted (glutathione-S-transferase and heat shock protein 27/28 kDa). The varied nature of the proteins identified suggests that epidermal keratinocytes have physiologic functions that have yet to be identified.
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PMID:A partial catalog of proteins secreted by epidermal keratinocytes in culture. 1023 78

Expression of differentiation and adhesion cell surface antigens (LewisX - CD15, CD44, syndecan 1 - CD138 and basigin/EMMPRIN - CD147) were determined on the cell surface of human breast carcinoma MCF7 cells in vitro with the aid of flow cytometry and compared with that of MCF-7/6 cells, with functionally defective E-cadherin system and increased biological aggressiveness. The major cell surface alterations in MCF-7/6 cells compared with the parental MCF-7 cell line were a markedly increased CD15 (LewisX) and CD44 antigen cell surface expression on MCF-7/6 cells. There were no major differences between parental MCF-7 and MCF-7/6 cells in cell surface syndecan 1, basigin/EMMPRIN, E-cadherin and high affinity non-integrin laminin receptor expression. The constitutive cell surface gelatinase A and B activities were absent on MCF-7 and faint in MCF-7/6 cells. Both phorbol ester TPA and tumor necrosis factor TNF-alpha induced a marked up-regulation of gelatinase B only in MCF-7/6 cells. No marked differences in penetration of MCF-7 vs. MCF-7/6 cells into collagen/fibroblast matrix in vitro were observed. The increased expression of CD15 (LewisX), CD44 antigen and TNF-alpha-inducible gelatinase B on MCF-7/6 cells may represent auxiliary factors contributing to the increased biological aggressiveness of MCF-7/6 cells.
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PMID:Cell surface immunophenotype and gelatinase activity of the human breast carcinoma cell line (MCF-7/6) with functionally defective E-cadherin. 1035 28


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