Abstract:
:Amplification of the epidermal growth factor receptor (EGFR) gene is found in about 40% of glioblastomas (GBMs) but is rarely detected in GBM cell lines. We confirmed that the exceptional SKMG-3 GBM cell line retained amplified EGFR genes in vitro, and found that these sequences were concentrated on extra-chromosomal DNA particles similar to double-minute chromosomes. The cells contained two other gene mutations that are associated with high-grade astrocytic tumors: extra-chromosomal amplification of the cyclin-dependent kinase-4 (CDK4) gene and a homozygous mutation within the PTEN tumor suppressor gene. Immunoblots revealed very high levels of EGFR, moderately increased expression of CDK4, and no detectable PTEN protein. The overexpressed SKMG-3 EGFRs responded to exogenous ligand and resembled normal rather than mutant receptors. A heterozygous mutation of the p53 gene (p53R282W) correlated with failure of radiation to induce the expression of cyclin-dependent kinase inhibitor p21waf1 or an early G1 cell cycle arrest. Although each of these gene mutations occurs in GBMs, SKMG-3 cells had an unusual genotype in that a p53 gene mutation co-existed with amplified EGFR genes. Nonetheless, the SKMG-3 cell line can be exploited as a model to study how oncogenic EGFR signals in GBM cells interact with over-expressed CDK4 and loss of PTEN to confer the malignant phenotype.
journal_name
Acta Neuropatholjournal_title
Acta neuropathologicaauthors
Thomas C,Ely G,James CD,Jenkins R,Kastan M,Jedlicka A,Burger P,Wharen Rdoi
10.1007/s004010000332subject
Has Abstractpub_date
2001-06-01 00:00:00pages
605-15issue
6eissn
0001-6322issn
1432-0533journal_volume
101pub_type
杂志文章abstract::Immunohistochemical studies of monoamine neurons were performed to evaluate toxic effects of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) on young adult mice and compare them with those of their offspring. Mice, 9-11 weeks old (C57BL/6J), injected subcutaneously with a large dose of MPTP (17 mg/kg per day) duri...
journal_title:Acta neuropathologica
pub_type: 杂志文章
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abstract::A 50-year-old carpenter died in Western Pennsylvania of rabies on January 4, 1979. He had been hospitalized in an intensive care unit for 28 days. The diagnosis was made postmortem from light and electron microscopic examination of central nervous system tissue. Immunofluorescence studies confirmed the diagnosis later...
journal_title:Acta neuropathologica
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journal_title:Acta neuropathologica
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journal_title:Acta neuropathologica
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doi:10.1007/s00401-003-0719-9
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journal_title:Acta neuropathologica
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journal_title:Acta neuropathologica
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journal_title:Acta neuropathologica
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journal_title:Acta neuropathologica
pub_type: 杂志文章
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journal_title:Acta neuropathologica
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doi:10.1007/BF00691995
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journal_title:Acta neuropathologica
pub_type: 杂志文章
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journal_title:Acta neuropathologica
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journal_title:Acta neuropathologica
pub_type: 杂志文章
doi:10.1007/s00401-003-0797-8
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journal_title:Acta neuropathologica
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journal_title:Acta neuropathologica
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journal_title:Acta neuropathologica
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journal_title:Acta neuropathologica
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journal_title:Acta neuropathologica
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abstract::The calcium-activated protease calpain cleaves a variety of biologically important proteins and serves, therefore, as a key regulator of many cellular functions. Activation of both main isoforms, calpain 1 and calpain 2, was demonstrated previously in Alzheimer's disease. In this report, antibodies specifically recogn...
journal_title:Acta neuropathologica
pub_type: 杂志文章
doi:10.1007/s00401-002-0528-6
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journal_title:Acta neuropathologica
pub_type: 杂志文章
doi:10.1007/s00401-005-1015-7
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journal_title:Acta neuropathologica
pub_type: 杂志文章
doi:10.1007/BF00690561
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journal_title:Acta neuropathologica
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abstract::This study tests the effects of chronic electrostimulation on denervated/reinnervated skeletal muscle in producing an optimal restoration of size and mechanical and histochemical properties. We compared tibialis anterior muscles in four groups of rats: in unoperated control (C) and 10 weeks following nerve lesion with...
journal_title:Acta neuropathologica
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journal_title:Acta neuropathologica
pub_type: 杂志文章
doi:10.1007/BF00309632
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journal_title:Acta neuropathologica
pub_type: 杂志文章
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