Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:2.7.11.13 (protein kinase C)
 49,245 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The proliferation of many nonglial tumors in vitro depends on the presence of nanomolar concentrations of one or more growth factors. To define the growth factor requirements of malignant glial tumors, the authors examined the response properties of four low-passage human malignant glioma lines to the following mitogens: epidermal growth factor (EGF), acidic and basic fibroblast growth factors (FGF's), insulin-like growth factor I (IGF-I), nerve growth factor (NGF), platelet-derived growth factor (PDGF), 12-O-tetradecanoyl-13-phorbol acetate (TPA), and serum. Each of the tumors showed increased deoxyribonucleic acid (DNA) synthesis (assessed by acid-precipitable [3H]-thymidine incorporation) in response to PDGF with a maximum effect at 50 ng/ml. Three tumors responded to EGF, three to IGF-I, two to acidic FGF, two to basic FGF, and two to TPA with maximum effects at 10, 50, 1, 1, and 10 ng/ml, respectively. None of the tumors responded to NGF. In the responsive tumors, optimum concentrations of EGF, IGF, TPA, acidic FGF, and basic FGF induced, at most, a two- to fourfold increase in [3H]-thymidine incorporation, which was only 30% to 50% of the response seen in 10% serum. In contrast, PDGF increased DNA synthesis eight- to 10-fold, equaling the effect of 10% serum. Measurements of cell proliferation also demonstrated a significant response to PDGF in each of the tumors. Appropriate concentrations of an anti-PDGF neutralizing antibody inhibited baseline DNA synthesis and proliferation in the absence of added growth factors, suggesting the possible role of PDGF in autocrine stimulation of these cells. However, this antibody produced only slight inhibition of serum-induced mitogenesis. Trapidil, an agent reported to inhibit the effects of PDGF, and polymyxin B, an inhibitor of protein kinase C, strongly inhibited baseline as well as PDGF- and serum-induced mitogenesis. It is concluded that, in the malignant gliomas studied, PDGF may be acting as a dominant mitogen to enhance DNA synthesis, and may function in autocrine stimulation. However, other factors contained in serum can also contribute to cell division.
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PMID:Response of low-passage human malignant gliomas in vitro to stimulation and selective inhibition of growth factor-mediated pathways. 164 72

Trapidil is a PDGF antagonist that can inhibit the proliferation of the PDGF-producing glioma cells, U251MG. As the mechanism of growth-regulation by trapidil remains unclear, we studied its effect on the growth of U251MG cells. We performed a cell cycle analysis and examined the intracellular transduction pathway and oncogene expression in serum-stimulated glioma cells with or without trapidil. After the serum starvation for 3 days, glioma cell proliferation was stimulated by the addition of serum. Cell cycle analysis showed that cell cycle perturbations induced by trapidil included a decreased transition rate from G0-G1 to S phase, suggesting that some metabolic event is required for progress through the G0-G1 phase and that this event is sensitive to trapidil. Internal signal transduction mechanisms are central in the molecular control of cell growth. One such regulator is the protein kinase C(PKC) system and the c-fos gene is likely to be a direct target of intracellular signal transduction pathways. Therefore, we hypothesize that the intracellular PKC activity and c-fos expression of the trapidil-treated cells are suppressed. We posit that trapidil affects the intracellular signal transduction pathway PKC activity and c-fos expression in cells stimulated with serum containing growth factors.
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PMID:The mechanism of growth-regulation of glioma cells by trapidil. 767 82