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)

Proteome analysis of human umbilical endothelial cells was performed to identify proteins that are modified during vascular endothelial cell growth factor (VEGF)-induced transition from the quiescent into the proliferating-migrative phenotype. Subtractive analysis of two-dimensional gel patterns of human endothelial cells, before and after stimulation with VEGF(165), revealed differences in 85 protein spots. All proteins were identified by peptide sequencing and peptide mass fingerprinting using an electrospray spectrometer. The proteins identified were members of specific families including Ca(2+)-binding proteins, fatty-acid binding proteins, structural proteins, and chaperones. Remarkably, there was a massive activation of cellular machinery for both protein synthesis and protein degradation. Thus, among up-regulated proteins there were members of all groups of heat shock proteins (HSPs; HSP 27, HSP 60, HSP 70p5, HSP 70p8, HSP 90, and HSP 96) and some other proteins showing either chaperone activity or which participate in assembly of multimolecular structures (TCP-1, desmoplakins, junction plakoglobin, GRP 94, thioredoxin related protein, and peptidylprolyl isomerase). The increased expression of HSPs was confirmed at the mRNA level at different stages of treatment with VEGF. Similarly, components of the proteolytic machinery for the degradation of misfolded proteins (ER-60, cathepsin D, proteasome subunits, and protease inhibitor 6) were also up-regulated. On the other hand, changes in the expression of structural proteins (T-plastin, vimentin, alpha tubulin, actin, and myosin) could account, at least in part, for the different morphologies displayed by migrating endothelial cells. In summary, our data show that VEGF levels similar to those during physiological stresses induce a number of genes and multiple endogenous pathways seem to be engaged in restoring cellular homeostasis. To ensure cell survival, the molecular chaperones (the heat shock family of stress proteins) are highly up-regulated providing protein-folding machinery to repair or degrade misfolded proteins.
 ...
PMID:Heat shock proteins and other components of cellular machinery for protein synthesis are up-regulated in vascular endothelial cell growth factor-activated human endothelial cells. 1576 53

Thymidine phosphorylase (TP)/platelet-derived endothelial cell growth factor, stimulates chemataxis of endothelial cells and is involved in the angiogenesis of human solid tumours. In this study we investigated tissue sections from 93 breast carcinomas for the immunohistochemical expression of thymidine phosphorylase protein and in relationship to several clinicopathological parameters. The possible relationship to tumour neovascularization, VEGF expression, extracellular matrix components (tenascin, fibronectin, collagen type IV and laminin) and cathepsin D was also estimated. Nuclear and/or cytoplasmic TP expression was observed in tumour cells. Immunoreactivity was also often present in the stroma, endothelium and tumour-associated macrophages. High cytoplasmic TP expression, was observed in 35.5%, moderate in 30.1%, mild in 18.3%, while 16.1% of the cases were negative for TP expression. Moderate and high nuclear TP expression was observed in 30.1% of the tumours, low in 43%, while 26.9% did not show nuclear TP expression. High tumour stroma TP expression was expressed in 23.7% of the cases, moderate in 21.5%, mild in 45.2%, while 9.7% did not show stromal TP expression. TP expression did not correlate with the conventional clinicopathological features as well as with the microvessel density and the VEGF expression. Patients with high levels of tumour cell TP expression were significantly associated with a favorable outcome in univariate method of analysis. A positive correlation of TP expression with Cathepsin D expression was noticed. In addition, tumour cell TP expression was correlated with the extracellular matrix component tenascin, while stromal cell TP expression was correlated with the growth fraction of the tumour. Our data suggests that TP expression does not seem to affect directly the neovasculatur of breast carcinoma, although it seems to be implicated in the remodeling of breast cancer tissue, through the interaction with other extracellular matrix components or proteolytic enzymes. In addition, tumour cell TP expression could be considered as a prognostic indicator of breast cancer patients.
 ...
PMID:Thymidine phoshorylase expression in breast cancer: the prognostic significance and its association with other angiogenesis related proteins and extracellular matrix components. 1799 75