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Glioblastoma-related gene mutations and over-expression of functional epidermal growth factor receptors in SKMG-3 glioma cells.

Publication ,  Journal Article
Thomas, C; Ely, G; James, CD; Jenkins, R; Kastan, M; Jedlicka, A; Burger, P; Wharen, R
Published in: Acta Neuropathol
June 2001

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.

Duke Scholars

Published In

Acta Neuropathol

DOI

ISSN

0001-6322

Publication Date

June 2001

Volume

101

Issue

6

Start / End Page

605 / 615

Location

Germany

Related Subject Headings

  • Tumor Cells, Cultured
  • Signal Transduction
  • Phenotype
  • Neurology & Neurosurgery
  • Mutation
  • In Situ Hybridization
  • Humans
  • Glioblastoma
  • Genotype
  • Genes, p53
 

Citation

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MLA
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Thomas, C., Ely, G., James, C. D., Jenkins, R., Kastan, M., Jedlicka, A., … Wharen, R. (2001). Glioblastoma-related gene mutations and over-expression of functional epidermal growth factor receptors in SKMG-3 glioma cells. Acta Neuropathol, 101(6), 605–615. https://doi.org/10.1007/s004010000332
Thomas, C., G. Ely, C. D. James, R. Jenkins, M. Kastan, A. Jedlicka, P. Burger, and R. Wharen. “Glioblastoma-related gene mutations and over-expression of functional epidermal growth factor receptors in SKMG-3 glioma cells.Acta Neuropathol 101, no. 6 (June 2001): 605–15. https://doi.org/10.1007/s004010000332.
Thomas C, Ely G, James CD, Jenkins R, Kastan M, Jedlicka A, et al. Glioblastoma-related gene mutations and over-expression of functional epidermal growth factor receptors in SKMG-3 glioma cells. Acta Neuropathol. 2001 Jun;101(6):605–15.
Thomas, C., et al. “Glioblastoma-related gene mutations and over-expression of functional epidermal growth factor receptors in SKMG-3 glioma cells.Acta Neuropathol, vol. 101, no. 6, June 2001, pp. 605–15. Pubmed, doi:10.1007/s004010000332.
Thomas C, Ely G, James CD, Jenkins R, Kastan M, Jedlicka A, Burger P, Wharen R. Glioblastoma-related gene mutations and over-expression of functional epidermal growth factor receptors in SKMG-3 glioma cells. Acta Neuropathol. 2001 Jun;101(6):605–615.
Journal cover image

Published In

Acta Neuropathol

DOI

ISSN

0001-6322

Publication Date

June 2001

Volume

101

Issue

6

Start / End Page

605 / 615

Location

Germany

Related Subject Headings

  • Tumor Cells, Cultured
  • Signal Transduction
  • Phenotype
  • Neurology & Neurosurgery
  • Mutation
  • In Situ Hybridization
  • Humans
  • Glioblastoma
  • Genotype
  • Genes, p53