Genetic characterization of commonly used glioma cell lines in the rat animal model system.
OBJECTIVE
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.
Sibenaller
Zita A
ZA
Department of Neurosurgery, University of Iowa Hospitals, Iowa City, Iowa 52242, USA.
Etame
Arnold B
AB
Ali
Mushtaq M
MM
Barua
Manali
M
Braun
Terry A
TA
Casavant
Thomas L
TL
Ryken
Timothy C
TC
D000818:Animals; D000831:Animals, Newborn; D001253:Astrocytes / Q000378:metabolism*; D014408:Biomarkers, Tumor / Q000235:genetics*; D001932:Brain Neoplasms / Q000175:diagnosis / Q000235:genetics*; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D002471:Cell Transformation, Neoplastic / Q000235:genetics / Q000378:metabolism; D004195:Disease Models, Animal; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic / Q000235:genetics*; D005910:Glioma / Q000175:diagnosis / Q000235:genetics*; D009361:Neoplasm Invasiveness / Q000235:genetics; D009389:Neovascularization, Pathologic / Q000235:genetics; D009419:Nerve Tissue Proteins / Q000235:genetics; D020411:Oligonucleotide Array Sequence Analysis; D039904:Pluripotent Stem Cells / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley
D014408:Biomarkers, Tumor; D009419:Nerve Tissue Proteins