Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.4.24.3 (collagenase)
 18,340 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

E-cadherin is a transmembrane glycoprotein which mediates epithelial cell-to-cell adhesion function as a tumor suppressor and frequently loss of expression in a wide spectrum of human cancer. However, recent studies demonstrated that E-cadherin was always over-expressed in inflammatory breast cancer (IBC) specimen and cell lines, which is a clinical extreme malignancy of breast cancer. It is hypothesized that the gain and not the loss of the E-cadherin axis contributes to the IBC unique phenotype. To test this assumption, we generated dominant negative mutant E-cadherin high-expression inflammatory breast cancer cells by introduced dominant negative mutant E-cadherin (H-2kd-E-cad) cDNA into human IBC SUM149 cells. Our studies demonstrated that the ability of invasion of SUM149 cells was significantly inhibited by H-2kd-E-cad via down-regulation of MMP-1 and MMP-9 expression. The underlying signal pathway of MAPK phosphorylated Erk 1/2(P44/42) in H-2kd-E-cad-transfected SUM149 cells was significantly down-regulated compared to parental and mock contrast. Our studies provided further functional evidence as the gain of E-cadherin expression dedicated to the IBC malignant phenotype and the blockage of MAPK/Erk activation maybe a promising therapeutic target.
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PMID:Dominant-negative E-cadherin inhibits the invasiveness of inflammatory breast cancer cells in vitro. 1693 44

Inflammatory breast cancer (IBC) represents the most aggressive form of breast cancer, characterized by rapid progression, involvement of dermal lymphatic emboli and extensive metastatic lymph nodes. Matrix metalloproteinases (MMPs) are proteolytic enzymes that play an important role in cancer invasion and metastasis. Although the role of MMPs in non-IBC is well studied, little is known about its role in IBC. Thus the goal of the present study was to 1) investigate the expression and activity levels of membrane type matrix metalloproteinase-1 (MT1-MMP) and matrix metalloproteinase-2 and-9 (MMP-2 and MMP-9) in IBC versus non-IBC tissue samples and; 2) test correlation between expression of MT1-MMP and pro- and active forms of MMP-2 and MMP-9. We enrolled 51 breast cancer patients, 21 were diagnosed as IBC and 30 as non-IBC. Level of expression of MT1-MMP in carcinoma tissue was assessed by immunoblot and immunohistochemistry techniques. The expression and activation of MMP-2 and MMP-9 was measured by gelatin zymography. Our results revealed that MT1-MMP, pro-MMP-2, pro-MMP-9 and active MMP-2 were more expressed in IBC tissue versus non-IBC. Furthermore, we found that MT1-MMP expression correlates with expression of pro-MMP-2, pro-MMP-9 and active MMP-2 in IBC tissue samples and with MMP-9 in non-IBC tissue sample. In conclusion, our study suggests a role of MT1-MMP in inflammatory breast cancer disease progression.
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PMID:Membrane type-1 matrix metalloproteinase (MT1-MMP) correlates with the expression and activation of matrix metalloproteinase-2 (MMP-2) in inflammatory breast cancer. 2214 May 98