Glioma cell motility is associated with reduced transcription of proapoptotic and proliferation genes: A cDNA microarray analysis

L. Mariani, C. Beaudry, W. S. McDonough, D. B. Hoelzinger, T. Demuth, K. R. Ross, T. Berens, S. W. Coons, G. Watts, J. M. Trent, J. S. Wei, A. Giese, M. E. Berens

Research output: Contribution to journalArticle

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 5700 and 7000 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), PLCγ, and CD44, were over expressed; other genes, like adducin 3γ 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.

Original languageEnglish (US)
Pages (from-to)161-176
Number of pages16
JournalJournal of Neuro-Oncology
Volume53
Issue number2
DOIs
StatePublished - 2001
Externally publishedYes

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Microarray Analysis
Oligonucleotide Array Sequence Analysis
Glioma
Cell Movement
Complementary DNA
Genes
Cellular Structures
Extracellular Matrix
Neuropilin-2
Genetic Transcription
Effector Caspases
Apoptosis
Cyclin B
Tenascin
Cyclin A
Cell Line
Extracellular Matrix Proteins
Proliferating Cell Nuclear Antigen
Gene Expression Profiling
Glioblastoma

Keywords

  • Apoptosis
  • cDNA microarray
  • Glioma
  • Migration
  • Proliferation

ASJC Scopus subject areas

  • Clinical Neurology
  • Cancer Research
  • Oncology
  • Neuroscience(all)

Cite this

Mariani, L., Beaudry, C., McDonough, W. S., Hoelzinger, D. B., Demuth, T., Ross, K. R., ... Berens, M. E. (2001). Glioma cell motility is associated with reduced transcription of proapoptotic and proliferation genes: A cDNA microarray analysis. Journal of Neuro-Oncology, 53(2), 161-176. https://doi.org/10.1023/A:1012253317934

Glioma cell motility is associated with reduced transcription of proapoptotic and proliferation genes : A cDNA microarray analysis. / Mariani, L.; Beaudry, C.; McDonough, W. S.; Hoelzinger, D. B.; Demuth, T.; Ross, K. R.; Berens, T.; Coons, S. W.; Watts, G.; Trent, J. M.; Wei, J. S.; Giese, A.; Berens, M. E.

In: Journal of Neuro-Oncology, Vol. 53, No. 2, 2001, p. 161-176.

Research output: Contribution to journalArticle

Mariani, L, Beaudry, C, McDonough, WS, Hoelzinger, DB, Demuth, T, Ross, KR, Berens, T, Coons, SW, Watts, G, Trent, JM, Wei, JS, Giese, A & Berens, ME 2001, 'Glioma cell motility is associated with reduced transcription of proapoptotic and proliferation genes: A cDNA microarray analysis', Journal of Neuro-Oncology, vol. 53, no. 2, pp. 161-176. https://doi.org/10.1023/A:1012253317934
Mariani, L. ; Beaudry, C. ; McDonough, W. S. ; Hoelzinger, D. B. ; Demuth, T. ; Ross, K. R. ; Berens, T. ; Coons, S. W. ; Watts, G. ; Trent, J. M. ; Wei, J. S. ; Giese, A. ; Berens, M. E. / Glioma cell motility is associated with reduced transcription of proapoptotic and proliferation genes : A cDNA microarray analysis. In: Journal of Neuro-Oncology. 2001 ; Vol. 53, No. 2. pp. 161-176.
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AU - Beaudry, C.

AU - McDonough, W. S.

AU - Hoelzinger, D. B.

AU - Demuth, T.

AU - Ross, K. R.

AU - Berens, T.

AU - Coons, S. W.

AU - Watts, G.

AU - Trent, J. M.

AU - Wei, J. S.

AU - Giese, A.

AU - Berens, M. E.

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AB - 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 5700 and 7000 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), PLCγ, and CD44, were over expressed; other genes, like adducin 3γ 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.

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