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Activation of Apoptosis by Cytoplasmic Microinjection of Cytochrome c
Published on: June 29, 2011
Coexpression of genes involved in apoptosis in central nervous system neoplasms
C S Bruggers1, D Fults, S L Perkins
1Department of Pediatrics, Huntsman Cancer Institute, University of Utah School of Medicine, Salt Lake City, USA.
Purpose:
Apoptosis plays a crucial role in normal development and mediates tumor response to chemotherapy. This study investigated the pattern of apoptotic gene expression in brain tumor tissue specimens and cell lines.
Materials And Methods:
BCL2, BCLXL, BCLXS, and BAX transcripts were amplified using reverse transcriptase polymerase chain reaction in 7 high-grade gliomas (HGGs), 7 ependymomas, and 6 cell lines (2 glioblastomas, 3 medulloblastomas, and 1 supratentorial-primitive neuroectodermal tumor [PNET]). Immunohistochemical staining for BCL2, BCLX, BAX, and p53 was performed in 7 pediatric low-grade gliomas (LGGs) and 7 pediatric HGGs.
Results:
Six of seven gliomas, all ependymomas, and all glioblastoma and medulloblastoma cell lines expressed BCLXL and BAX. BCL2 expression was only detected in the supratentorial PNET line PFSK. BCLXS was absent in all tumors. By immunohistochemistry, no glial tumors stained positively for BCL2. Similar BAX and BCLX protein expression was observed in LGG and HGG. Three of five glioblastomas showed significant p53 expression.
Conclusions:
Coexpression of proapoptotic and antiapoptotic genes in human brain tumors supports the hypothesis that the relative expression of competing genes determines apoptotic threshold.
Insights
Brain tumors show coexpression of genes that promote and inhibit apoptosis. The balance between these genes influences the cell death threshold, impacting treatment response.
Area of Science:
- Molecular Biology
- Oncology
- Neuroscience
Background:
- Apoptosis is vital for development and cancer therapy.
- Understanding apoptotic gene expression in brain tumors is critical.
Purpose of the Study:
- Investigate apoptotic gene expression patterns in brain tumor tissues and cell lines.
- Analyze the expression of BCL2, BCLXL, BCLXS, and BAX.
Main Methods:
- Reverse transcriptase polymerase chain reaction (RT-PCR) for gene transcripts.
- Immunohistochemical staining for protein expression.
- Analysis of high-grade gliomas, ependymomas, glioblastomas, medulloblastomas, PNET, LGGs, and HGGs.
Main Results:
- BCLXL and BAX were widely expressed in most brain tumors and cell lines.
- BCL2 expression was limited to a single PNET cell line; absent in glial tumors.
- BAX and BCLX protein levels were similar in low-grade and high-grade gliomas; p53 was elevated in some glioblastomas.
Conclusions:
- Coexpression of proapoptotic and antiapoptotic genes is common in human brain tumors.
- The relative balance of competing apoptotic genes likely dictates the apoptotic threshold.
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