Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
16
pubmed:dateCreated
2008-4-14
pubmed:abstractText
A cancer stem cell population in malignant brain tumors takes an essential part in brain tumor initiation, growth, and recurrence. Growth factors, such as epidermal growth factor, fibroblast growth factor-2, vascular endothelial growth factor, platelet-derived growth factor, and hepatocyte growth factor, are shown to support the proliferation of neural stem cells and also may play key roles in gliomagenesis. However, the responsible growth factor(s), which controls maintenance of brain tumor stem cells, is not yet uncovered. We have established three cancer stem cell lines from human gliomas. These cells were immunoreactive with the neuronal progenitor markers, nestin and CD133, and established tumors that closely resembled the features of original tumor upon transplantation into mouse brain. Three cell lines retained their self-renewal ability and proliferation only in the presence of epidermal growth factor (>2.5 ng/ml). In sharp contrast, other growth factors, including fibroblast growth factor-2, failed to support maintenance of these cells. The tyrosine kinase inhibitors of epidermal growth factor signaling (AG1478 and gefitinib) suppressed the proliferation and self-renewal of these cells. Gefitinib inhibited phosphorylation of epidermal growth factor receptor as well as Akt kinase and extracellular signal-regulated kinase 1/2. Flow cytometric analysis revealed that epidermal growth factor concentration-dependently increased the population of CD133-positive cells. Gefitinib significantly reduced CD133-positive fractions and also induced their apoptosis. These results indicate that maintenance of human brain tumor stem cells absolutely requires epidermal growth factor and that tyrosine kinase inhibitors of epidermal growth factor signaling potentially inhibit proliferation and induce apoptosis of these cells.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
http://linkedlifedata.com/resource/pubmed/chemical/AC133 antigen, http://linkedlifedata.com/resource/pubmed/chemical/Antigens, CD, http://linkedlifedata.com/resource/pubmed/chemical/Enzyme Inhibitors, http://linkedlifedata.com/resource/pubmed/chemical/Epidermal Growth Factor, http://linkedlifedata.com/resource/pubmed/chemical/Glycoproteins, http://linkedlifedata.com/resource/pubmed/chemical/Intercellular Signaling Peptides..., http://linkedlifedata.com/resource/pubmed/chemical/Peptides, http://linkedlifedata.com/resource/pubmed/chemical/Protein-Tyrosine Kinases, http://linkedlifedata.com/resource/pubmed/chemical/Quinazolines, http://linkedlifedata.com/resource/pubmed/chemical/Tyrphostins, http://linkedlifedata.com/resource/pubmed/chemical/gefitinib, http://linkedlifedata.com/resource/pubmed/chemical/tyrphostin AG 1478
pubmed:status
MEDLINE
pubmed:month
Apr
pubmed:issn
0021-9258
pubmed:author
pubmed:issnType
Print
pubmed:day
18
pubmed:volume
283
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
10958-66
pubmed:dateRevised
2009-11-19
pubmed:meshHeading
pubmed-meshheading:18292095-Antigens, CD, pubmed-meshheading:18292095-Brain Neoplasms, pubmed-meshheading:18292095-Enzyme Inhibitors, pubmed-meshheading:18292095-Epidermal Growth Factor, pubmed-meshheading:18292095-Gene Expression Regulation, Neoplastic, pubmed-meshheading:18292095-Glycoproteins, pubmed-meshheading:18292095-Humans, pubmed-meshheading:18292095-Intercellular Signaling Peptides and Proteins, pubmed-meshheading:18292095-Models, Biological, pubmed-meshheading:18292095-Peptides, pubmed-meshheading:18292095-Phosphorylation, pubmed-meshheading:18292095-Protein-Tyrosine Kinases, pubmed-meshheading:18292095-Quinazolines, pubmed-meshheading:18292095-Signal Transduction, pubmed-meshheading:18292095-Stem Cells, pubmed-meshheading:18292095-Tumor Cells, Cultured, pubmed-meshheading:18292095-Tyrphostins
pubmed:year
2008
pubmed:articleTitle
Epidermal growth factor plays a crucial role in mitogenic regulation of human brain tumor stem cells.
pubmed:affiliation
Department of Neurosurgery, Tissue and Organ Development Regeneration and Advanced Medical Science, and Cell Signaling, Gifu University Graduate School of Medicine, Gifu 501-1194, Japan. akio.soeda@gmail.com
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't