Increased expression of genes from growth factor signaling pathways in glioblastoma cell lines.
The concept of autocrine stimulation of cell proliferation postulates growth autonomy by acquisition of the ability to produce and respond to growth factors. Overproduction of several growth factors in a variety of human tumors and cell lines derived from these tumors has been reported. We have screened several cell lines derived from glioblastomas for anomalies in the expression of genes encoding transforming growth factor alpha (TGF-alpha), TGF-beta, basic fibroblast growth factor (bFGF) and its high-affinity receptor, flg. Compared with normal human brain tissue, we observed a generalized elevation in the levels of expression of these genes in glioblastoma cell lines and an SV40-transformed human astroglial cell line. Overexpression of these genes does not appear to be merely a reflection of the proliferative state of transformed cells since some other human tumor cell lines, when analysed for the expression of TGF-beta and bFGF, did not show a significant increase in these transcripts. The specificity of the elevated transcription of TGF-alpha, TGF-beta, bFGF and flg in glioblastoma cell lines is further suggested by the fact that the transcription of the proto-oncogene c-erbB2, which is overproduced in breast tumor cell lines, was not elevated in glioblastoma cell lines. Increased expression of growth factors, which are potent mitogens and angiogens, and/or their receptors may have critical roles in autonomous proliferation as well as neovascularization of glioblastomas.
Saxena
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Surgical Neurology Branch, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, Maryland 20892.
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D016222:Fibroblast Growth Factor 2 / Q000235:genetics; D000091344:Filaggrin Proteins; D015870:Gene Expression / Q000187:drug effects; D005910:Glioma / Q000235:genetics*; D006133:Growth Substances / Q000494:pharmacology*; D006801:Humans; D066298:In Vitro Techniques; D000090063:Proto-Oncogene Mas; D011518:Proto-Oncogene Proteins / Q000235:genetics; D012333:RNA, Messenger / Q000235:genetics; D012334:RNA, Neoplasm / Q000235:genetics; D018719:Erb-b2 Receptor Tyrosine Kinases; D011956:Receptors, Cell Surface / Q000235:genetics; D017468:Receptors, Fibroblast Growth Factor; D015291:Transforming Growth Factors / Q000235:genetics; D014407:Tumor Cells, Cultured
D016222:Fibroblast Growth Factor 2; D000091344:Filaggrin Proteins; D006133:Growth Substances; D000090063:Proto-Oncogene Mas; D011518:Proto-Oncogene Proteins; D012333:RNA, Messenger; D012334:RNA, Neoplasm; D018719:Erb-b2 Receptor Tyrosine Kinases; D011956:Receptors, Cell Surface; D017468:Receptors, Fibroblast Growth Factor; D015291:Transforming Growth Factors; C000717249:FLG protein, human; C000715470:MAS1 protein, human