title: Glioma cell motility is associated with reduced transcription of proapoptotic and proliferation genes: a cDNA microarray analysis.
abstract: Microarray analysis of complementary DNA (cDNA) allows large-scale, comparative, gene expression profiling of two different cell populations. This approach has the potential for elucidating the primary transcription events and genetic cascades responsible for increased glioma cell motility in vitro and invasion in vivo. These genetic determinants could become therapeutic targets. We compared cDNA populations of a glioma cell line (G112) exposed or not to a motility-inducing substrate of cell-derived extracellular matrix (ECM) proteins using two sets of cDNA microarrays of 5,700 and 7,000 gene sequences. The data were analyzed considering the level and consistency of differential expression (outliers) and whether genes involved in pathways of motility, apoptosis, and proliferation were differentially expressed when the motility behavior was engaged. Validation of differential expression of selected genes was performed on additional cell lines and human glioblastoma tissue using quantitative RT-PCR. Some genes involved in cell motility, like tenascin C, neuropilin 2, GAP43, PARG1 (an inhibitor of Rho), PLCy, and CD44, were over expressed; other genes, like adducin 3y and integrins, were down regulated in migrating cells. Many key cell cycle components, like cyclin A and B, and proliferation markers, like PCNA, were strongly down regulated on ECM. Interestingly, genes involved in apoptotic cascades, like Bcl-2 and effector caspases, were differentially expressed, suggesting the global down regulation of proapoptotic components in cells exposed to cell-derived ECM. Overall, our findings indicate a reduced proliferative and apoptotic activity of migrating cells. cDNA microarray analysis has the potential for uncovering genes linking the phenotypic aspects of motility, proliferation, and apoptosis.
authors.affiliation: Neuro-Oncology Laboratory, Barrow Neurological Institute, Phoenix, AZ, USA.
authors.forename: L
authors.initials: L
authors.lastname: Mariani
authors.forename: C
authors.initials: C
authors.lastname: Beaudry
authors.forename: W S
authors.initials: WS
authors.lastname: McDonough
authors.forename: D B
authors.initials: DB
authors.lastname: Hoelzinger
authors.forename: T
authors.initials: T
authors.lastname: Demuth
authors.forename: K R
authors.initials: KR
authors.lastname: Ross
authors.forename: T
authors.initials: T
authors.lastname: Berens
authors.forename: S W
authors.initials: SW
authors.lastname: Coons
authors.forename: G
authors.initials: G
authors.lastname: Watts
authors.forename: J M
authors.initials: JM
authors.lastname: Trent
authors.forename: J S
authors.initials: JS
authors.lastname: Wei
authors.forename: A
authors.initials: A
authors.lastname: Giese
authors.forename: M E
authors.initials: ME
authors.lastname: Berens
mesh_terms: D017209:Apoptosis / Q000235:genetics; D001932:Brain Neoplasms / Q000737:chemistry / Q000473:pathology*; D018797:Cell Cycle Proteins / Q000096:biosynthesis / Q000235:genetics; D002465:Cell Movement / Q000187:drug effects / Q000235:genetics; D003199:Computer Systems; D003470:Culture Media / Q000494:pharmacology; D018076:DNA, Complementary / Q000235:genetics; D020224:Expressed Sequence Tags; D016326:Extracellular Matrix Proteins / Q000494:pharmacology; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D005909:Glioblastoma / Q000737:chemistry / Q000473:pathology; D005910:Glioma / Q000473:pathology*; D006133:Growth Substances / Q000096:biosynthesis / Q000235:genetics; D006801:Humans; D007834:Lasers; D009361:Neoplasm Invasiveness / Q000235:genetics*; D009363:Neoplasm Proteins / Q000096:biosynthesis* / Q000235:genetics; D020411:Oligonucleotide Array Sequence Analysis; D010641:Phenotype; D016133:Polymerase Chain Reaction; D019063:Tenascin / Q000096:biosynthesis / Q000235:genetics; D014158:Transcription, Genetic / Q000187:drug effects; D014407:Tumor Cells, Cultured / Q000187:drug effects / Q000378:metabolism / Q000473:pathology
chemical_list: D018797:Cell Cycle Proteins; D003470:Culture Media; D018076:DNA, Complementary; D016326:Extracellular Matrix Proteins; D006133:Growth Substances; D009363:Neoplasm Proteins; D019063:Tenascin