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cDNA array analysis of SPARC-modulated changes in glioma gene expression
William A Golembieski1, Sandra A Rempel
1Barbara Jane Levy Laboratory of Molecular Neuro-Oncology, Hermelin Brain Tumor Center, Department of Neurosurgery, Henry Ford Health Sciences Center, Detroit, MI 48202, USA.
Journal of Neuro-Oncology
|January 4, 2003
Summary
Secreted protein acidic and rich in cysteine (SPARC) promotes glioma invasion. Gene expression analysis revealed novel candidate genes involved in SPARC
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- Secreted protein acidic and rich in cysteine (SPARC) is highly expressed in human gliomas.
- SPARC promotes glioma invasion and influences tumor growth.
- The impact of SPARC on intracellular signaling and gene expression in gliomas is not fully understood.
Purpose of the Study:
- To investigate the downstream gene expression changes induced by SPARC in glioma cells.
- To identify novel genes involved in SPARC-mediated glioma invasion and growth.
- To explore the potential of SPARC as a therapeutic target in gliomas.
Main Methods:
- Utilized a doxycycline-controlled gene expression system to manipulate SPARC levels in glioma cells.
- Performed cDNA array analyses to compare gene expression profiles between SPARC-expressing and non-expressing cells.
- Validated array findings using RT-PCR and Northern blot analyses in cell lines and human glioma tissues.
Main Results:
- SPARC manipulation led to significant upregulation and downregulation of numerous genes, with most being novel.
- Identified both reversible and irreversible gene expression changes in response to SPARC.
- Validated array results and confirmed differential gene expression in human glioma samples, highlighting BIGH3 and PAI-1.
Conclusions:
- cDNA array analyses identified candidate genes mediating SPARC's effects on glioma cell cycle, signaling, and migration.
- SPARC induces both reversible and irreversible gene expression alterations in gliomas.
- Further research into these candidate genes may elucidate SPARC's role and therapeutic potential in glioma.