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

摘要: Amplification of the epidermal growth factor receptor (EGFR) gene is found in about 40% glioblastomas (GBMs) but rarely detected GBM cell lines. We confirmed that exceptional SKMG-3 line retained amplified EGFR genes vitro, and these sequences were concentrated on extra-chromosomal DNA particles similar to double-minute chromosomes. The cells contained two other mutations are associated with high-grade astrocytic tumors: amplification cyclin-dependent kinase-4 (CDK4) a homozygous mutation within PTEN tumor suppressor gene. Immunoblots revealed very high levels EGFR, moderately increased expression CDK4, no detectable protein. over-expressed EGFRs responded exogenous ligand resembled normal rather than mutant receptors. A heterozygous p53 (p53R282W) correlated failure radiation induce kinase inhibitor p21waf1 or an early G1 cycle arrest. Although each occurs GBMs, had unusual genotype co-existed genes. Nonetheless, can be exploited as model study how oncogenic signals interact CDK4 loss confer malignant phenotype.