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)

In this study, we established hepatitis C virus (HCV) core-expressing mouse liver cells and investigated changes occurring in the gene expression profile accompanied by expression of the viral core protein using DNA array analysis. Both non-transformed and transformed mouse liver cells constitutively expressing the viral core protein were established by DNA transfection, and subjected to DNA array analysis. For the genes judged positive by DNA array, Northern blot analysis was done for corroboration. DNA array analysis revealed one up-regulated gene and three down-regulated genes by expression of the viral core protein in non-transformed liver cells. For the transformed liver cells, four enhanced and five suppressed genes were observed. The Northern blot corroboration analysis clarified two genes, osteopontin precursor and activating transcription factor 4, as being down-regulated by the viral core protein in both non-transformed and transformed liver cells, and three genes, cathepsin D, matrix metalloproteinase 14 and anti-proliferative B-cell translocation gene 2, as being up-regulated by the viral core protein in only transformed liver cells. In conclusion, a total of five genes were identified as viral core protein-responsive ones in the DNA array analysis. Alterations in the expression levels of these genes may be relevant to the viral core-mediated pathogenesis.
 ...
PMID:Changes in gene expression profile by HCV core protein in cultured liver cells: analysis by DNA array assay. 1269 50

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.
 ...
PMID:[Proteases by reactive stromal cells in cancer: an attractive therapeutic target]. 1698 Feb 37