Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.4.23.5 (cathepsin D)
 4,130 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We have compared by RNA in situ hybridisation on serial cryo-sections the distribution of cathepsin D (cathD), stromelysin 3 (strom-3), and urokinase plasminogen activator (UPA) gene expression in different tissues of human benign and malignant mammary tumors. Cath-D expression was found to be higher in adenocarcinomas compared to non-tumoral glands. The cath-D RNA was located in mammary epithelial cancer cells rather than in fibroblasts, indicating that the cath-D gene was overexpressed in cancer cells, where the corresponding protein determined by immunohistochemical staining had been shown to be accumulated (E Roger et al., Human Pathol 25: 863-871,1994). In contrast strom-3 RNA in adjacent tissue sections used as a control of tissue localisation was mostly expressed in peritumoral fibroblasts rather than in cancer cells confirming previous results of Basset et al. and validating our methodology. UPA RNA was detected both in tumor cells and in stromal cells. In benign lesions the 3 protease RNAs were mostly found in epithelial cells. Stromal cells expressed UPA RNA in 5 of 7 lesions, cath-D and strom-3 in only one sample. We conclude that in breast cancer patients, cath-D gene expression is increased in epithelial mammary cancer cells at the RNA level as well as at the protein level, suggesting an altered transcriptional regulation. In non malignant lesions, the distribution was different with a predominant distribution in epithelial mammary cells for the 3 protease messenger RNA.
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PMID:Cellular localisation by in situ hybridisation of cathepsin D, stromelysin 3, and urokinase plasminogen activator RNAs in breast cancer. 886 40

Oxytocin either increases or inhibits cell growth in different cell subtypes. We tested here the effect of oxytocin on cell proliferation and migration of human dermal microvascular endothelial cells (HMEC) and tumor-associated endothelial cells purified from human breast carcinomas (B-TEC). Oxytocin receptors were expressed in both cell subtypes at mRNA and protein levels. Through oxytocin receptor, oxytocin (1 nmol/L-1 mumol/L) significantly increased cell proliferation and migration in both HMEC and B-TEC, and addition of a selective oxytocin antagonist fully reverted these effects. To verify whether a different expression of adhesion molecule-related genes could be responsible for the oxytocin-induced cell migration, untreated and treated cells were compared applying a microarray technique. In HMEC, oxytocin induced the overexpression of the matrix metalloproteinase (MMP)-17, cathepsin D, and integrin beta(6) genes. In B-TEC, oxytocin significantly switched on the gene profile of some MMP (MMP-11 and MMP-26) and of integrin beta(6). The up-regulation of the integrin beta(6) gene could be involved in the oxytocin-induced cell growth, because this subunit is known to determine activation of mitogen-activated protein kinase-extracellular signal-regulated kinase 2, which is involved in the oxytocin mitogenic effect. In B-TEC, oxytocin also increased the expression of caveolin-1 at gene and protein levels. Because oxytocin receptor localization within caveolin-1-enriched membrane domains is necessary for activation of the proliferative (instead of the inhibitory) response to oxytocin, its enhanced expression can be involved in the oxytocin-induced B-TEC growth as well. Altogether, these data indicate that oxytocin contributes to cell motility and growth in HMEC and B-TEC.
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PMID:Oxytocin induces proliferation and migration in immortalized human dermal microvascular endothelial cells and human breast tumor-derived endothelial cells. 1677 82

Cancer-associated or reactive stromal cells are composed of endothelial and inflammatory cells as well as of spindle cells such as fibroblasts and myofibroblasts. In addition to participating to the tumor tissue frame, these cells contribute actively to tumor nutrition and progression through neo-angiogenesis and production of a variety of molecules including numerous proteases, of which a number (MMP14, MMP11, FAP and uPA) are almost exclusively produced by reactive stromal cells. Cancer cells interact with reactive stromal cells which involves a large number of proteases. Several molecules (TGFbeta, PDGF, EMMPRIN) produced by cancer cells induce the production of stromal proteases which in turn stimulate cancer cells through binding to a receptor (for example, MMP-2 and integrin alpha v beta 3). Our experience shows that protease overexpression by reactive stromal cells (cathepsin D, MMP-11, MMP-14) leads to an adverse clinical course in breast cancer. Phenotypic and genotypic differences were found between reactive stromal cells and fibroblasts of normal tissue and our research team found that reactive stromal cells also respond differently to similar stimulations in different individuals. These results support the hypothesis that the biologic behaviour of cancer is not only dependent on tumour characteristics but also on those of patients'stromal cells and that comparable tumours in two individuals may follow different clinical courses. These studies and our experience underscores the importance of characterising cancer-associated reactive stromal cells because of the therapeutic potential of this approach. Furthermore, reactive stromal cells should be genetically more stable that cancer cells and, in theory, should less likely develop mutations and treatment resistance.
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PMID:[Proteases by reactive stromal cells in cancer: an attractive therapeutic target]. 1698 Feb 37