Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0476089 (endometrial cancer)
 11,379 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The matrix metalloproteinases (MMPs) are a family of proteolytic enzymes, which are capable of degradation of the proteins composing the extracellular matrix and basement membrane. Their proteolytic activity depends on their binding to metal Zinc and is controlled by tissue inhibitors of MMP (TIMPs). Degradation of the extracellular matrix and basement membrane is an important component of the process of tumor invasiveness, progression, angiogenesis and metastatic spread. Since MMPs may serve as markers of tumor behavior and as predictors of survival and since synthetic inhibitors of MMP may have a place in the treatment of cancer, researching MMPs and their tissue inhibitors in malignant diseases has attracted growing attention. Studies on MMPs and their tissue inhibitors in malignancies of the female genital tract have shown the following: 1) In ovarian carcinoma and cervical carcinoma, over-expression of MMP-2 and MMP-9 is associated with invasiveness, metastatic spread and poor prognosis; 2) In endometrial carcinoma, MMP-7 (matrilysin) is the main MMP associated with invasiveness, metastatic spread and poor prognosis; 3) In cervical intra-epithelial neoplasia (CIN), measuring MMP-2 can assist in identifying high-risk for progression CIN I and CIN II; 4). In vulvar squamous cell carcinoma, over-expression of MMP-13 is associated with invasiveness, metastatic spread and poor prognosis. It is speculated that using synthetic drugs that inhibit MMPs in combination with conventional chemotherapy may contribute to the improvement of treatment results in cancer patients.
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PMID:[Matrix metalloproteinases and their tissue inhibitors in malignancies of the female genital tract]. 1463 13

Matrix metalloproteinase-7 (MMP-7) is upregulated during carcinogenesis and its expression correlates with metastasis of human endometrial and gastrointestinal carcinomas. In the present study, we have developed a new method to localize the activity of MMP-7 within tissues. Polyethylene terephthalate films were uniformly coated with crosslinked carboxymethylated transferrin (CCm-Tf) as a substrate and incubated with frozen tissue sections mounted on the films. CCm-Tf on the films was degraded selectively by MMP-7, but showed little or no susceptibility to MMP-1, -2, -3, -9, or -13; MT1-MMP; MT3-MMP; or ADAMTS4. Although some serine proteinases such as elastase also digested CCm-Tf, CCm-Tf films impregnated with serine proteinase inhibitors prevented the digestion. When frozen sections of human endometrial carcinoma and lung carcinoma tissues were incubated on CCm-Tf films or those treated with proteinase inhibitors, the activity was detected in the carcinoma cell nests, where MMP-7 was immunolocalized. The present in situ zymography using CCm-Tf may be a useful method to analyze the functions of MMP-7 in pathophysiological conditions.
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PMID:Development of in situ zymography to localize active matrix metalloproteinase-7 (matrilysin-1). 1595 27

Matrix metalloproteinase-7 (MMP-7, matrilysin- 1) modulates crucial biological events by processing many epithelial cell surface-associated effectors. We addressed MMP-7 interaction with human epithelial cells and its resulting activity. In human endometrium, a model of controlled tissue remodeling, proMMP-7 was diffusely immunolocalized inside epithelial cells, whereas MMP-7 delineated their entire plasma membrane. Endometrial explants preferentially retained active MMP-7, but not proMMP-7. Endometrial epithelial cells and carcinoma cells from various tissues bound active MMP-7. Endometrial carcinoma-derived Ishikawa cells showed high affinity (K(D) of approximately 2.5 nM) and capacity (approximately 260,000 sites per cell) for MMP-7. MMP-7 binding decreased by extracting membrane sterols or interfering with heparan sulfate proteoglycans, and was abrogated by tissue inhibitors of metalloproteinase-2 (TIMP-2) or synthetic MMP inhibitors. Bound MMP-7 not only remained fully active towards a macromolecular substrate but also became resistant to TIMP-2. We conclude that MMP-7-selective targeting to the plasma membrane of epithelial cells promotes its activity by conferring resistance to TIMP-2.
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PMID:Binding of matrilysin-1 to human epithelial cells promotes its activity. 1731 Feb 81

The human matrix metalloproteinase (MMP)-26, also called matrilysin-2 or endometase, has been isolated as a matrilysin (MMP-7) homolog. Several reports describe that MMP-26 may be related to the development of endometrial carcinomas. Total RNAs were isolated from 51 normal endometrial tissue samples, 6 endometrial hyperplasia tissue samples and 30 endometrial carcinomas. Real-time reverse transcription-polymerase chain reaction (RT-PCR) was performed to evaluate MMP-26 mRNA expression levels. We examined the effect of estrogen and its receptor (ER) on MMP-26 expression in endometrial carcinoma cell lines by real-time RT-PCR, western blot analysis and luciferase assays. To examine protein-DNA binding between ER and MMP-26 promoter, we performed chromatin immunoprecipitation (ChIP) assay. Real-time RT-PCR analysis revealed that MMP-26 mRNA expression was significantly higher in the normal human endometria and hyperplasias compared with that in endometrial carcinomas. Estrogen not only transactivated the MMP-26 promoter activity but also enhanced endogenous MMP-26 expression. The MMP-26 promoter region contains a putative ER response element (ERE). Nuclear ER protein interacted with ERE on the MMP-26 promoter by ChIP assay. We found a significant difference in MMP-26 expression in normal and malignant endometrial tissue samples and that estrogen induced MMP-26 expression. Estrogen may induce endometrial hyperplasia but not endometrial carcinoma. Our results provide evidence that regulation of MMP-26 promoter activity by estrogen may represent a mechanism for endometrial carcinogenesis.
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PMID:Estrogen and estrogen receptor induce matrix metalloproteinase-26 expression in endometrial carcinoma cells. 2375 74