Genetic characterization of commonly used glioma cell lines in the rat animal model system

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  • Departments of Neurosurgery and Biomedical Engineering, University of Iowa Hospitals and University of Iowa, Iowa City, Iowa; Department of Neurosurgery, University of Michigan, Ann Arbor, Michigan; and Department of Neurosurgery, University of Illinois at Chicago, Illinois
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Object

Animal models have been used extensively to discern the molecular biology of diseases and to gain insight into treatments. Nevertheless, discrepancies in the effects of treatments and procedures have been encountered during the transition from these animal models to application of the information to clinical trials in humans. To assess the genetic similarities between human gliomas and four cell lines used routinely in animal models, the authors used microarray technology to characterize the similarities and differences in gene expression.

Methods

To define the changes in gene expression, normal rat astrocytes were compared with four rat glioma cell lines (C6, 9L, F98, and RG2). The data were analyzed using two different methods: fold-change analysis and statistical analysis with t statistics. The gene products that were highlighted after intersecting the lists generated by the two methods of analysis were scrutinized against changes in gene expression reported in the literature. Tumorigenesis involves three major steps: the accumulation of genetic alterations, uncontrolled growth, and selected survival of transformed cells. The discussion of the results focuses attention on genes whose primary function is in pathways involved in glioma proliferation, infiltration, and neovascularization. A comparative microarray analysis of differentially expressed genes for four of the commonly used rat tumor cell lines is presented here.

Conclusions

Due to the variances between the cell lines and results from analyses in humans, caution must be observed in interpreting as well as in the translation of information learned from animal models to its application in human trials.

Abbreviations used in this paper:CDK = cyclin-dependent kinase; cDNA = complementary DNA; EGF = epidermal growth factor; EGFR = EGF receptor; FAK = focal adhesion kinase; FGF = fibrob-last growth factor; FGFR = FGF receptor; GBM = glioblastoma multiforme; HGF = hepatocyte growth factor; IGF = insulin growth factor; IGF-I, IGF-II = insulin-like growth factor–I and –II; MDR = multidrug resistant; MMP = matrix metalloproteinase; mRNA = messenger RNA; PDGF = platelet-derived growth factor; PDGFR = PDGF receptor; PLCγ = phospholipase C–gamma; Rb = retino-blastoma; RT-PCR = reverse transcription–polymerase chain reaction; TGFα = transforming growth factor–α; TIMP = tissue inhibitors of metalloproteinase; VEGF = vascular endothelial growth factor.

Object

Animal models have been used extensively to discern the molecular biology of diseases and to gain insight into treatments. Nevertheless, discrepancies in the effects of treatments and procedures have been encountered during the transition from these animal models to application of the information to clinical trials in humans. To assess the genetic similarities between human gliomas and four cell lines used routinely in animal models, the authors used microarray technology to characterize the similarities and differences in gene expression.

Methods

To define the changes in gene expression, normal rat astrocytes were compared with four rat glioma cell lines (C6, 9L, F98, and RG2). The data were analyzed using two different methods: fold-change analysis and statistical analysis with t statistics. The gene products that were highlighted after intersecting the lists generated by the two methods of analysis were scrutinized against changes in gene expression reported in the literature. Tumorigenesis involves three major steps: the accumulation of genetic alterations, uncontrolled growth, and selected survival of transformed cells. The discussion of the results focuses attention on genes whose primary function is in pathways involved in glioma proliferation, infiltration, and neovascularization. A comparative microarray analysis of differentially expressed genes for four of the commonly used rat tumor cell lines is presented here.

Conclusions

Due to the variances between the cell lines and results from analyses in humans, caution must be observed in interpreting as well as in the translation of information learned from animal models to its application in human trials.

Abbreviations used in this paper:CDK = cyclin-dependent kinase; cDNA = complementary DNA; EGF = epidermal growth factor; EGFR = EGF receptor; FAK = focal adhesion kinase; FGF = fibrob-last growth factor; FGFR = FGF receptor; GBM = glioblastoma multiforme; HGF = hepatocyte growth factor; IGF = insulin growth factor; IGF-I, IGF-II = insulin-like growth factor–I and –II; MDR = multidrug resistant; MMP = matrix metalloproteinase; mRNA = messenger RNA; PDGF = platelet-derived growth factor; PDGFR = PDGF receptor; PLCγ = phospholipase C–gamma; Rb = retino-blastoma; RT-PCR = reverse transcription–polymerase chain reaction; TGFα = transforming growth factor–α; TIMP = tissue inhibitors of metalloproteinase; VEGF = vascular endothelial growth factor.

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Contributor Notes

Address reprint requests to: Timothy C. Ryken, M.D., Department of Neurosurgery and Radiation Oncology, University of Iowa Hospitals and Clinics, Iowa City, Iowa 52242. email: timothy-ryken@uiowa.edu.

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