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Increased paired bo...
Increased paired box transcription factor 8 has a survival function in Glioma
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Hung, Noelyn (author)
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Chen, Yu-Jen (author)
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Taha, Ahmad (author)
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- Olivecrona, Magnus (author)
- Umeå universitet,Klinisk neurovetenskap
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Boet, Ronald (author)
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Wiles, Anna (author)
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Warr, Tracy (author)
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Shaw, Alisha (author)
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Eiholzer, Ramona (author)
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Baguley, Bruce C. (author)
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Eccles, Michael R. (author)
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Braithwaite, Antony W. (author)
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MacFarlane, Martin (author)
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Royds, Janice A. (author)
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Slatter, Tania (author)
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(creator_code:org_t)
- 2014-03-06
- 2014
- English.
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In: BMC Cancer. - : Springer Science and Business Media LLC. - 1471-2407. ; 14, s. 159-
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Abstract
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- Background:The molecular basis to overcome therapeutic resistance to treat glioblastoma remains unclear. The anti-apoptotic b cell lymphoma 2 (BCL2) gene is associated with treatment resistance, and is transactivated by the paired box transcription factor 8 (PAX8). In earlier studies, we demonstrated that increased PAX8 expression in glioma cell lines was associated with the expression of telomerase. In this current study, we more extensively explored a role for PAX8 in gliomagenesis.Methods:PAX8 expression was measured in 156 gliomas including telomerase-negative tumours, those with the alternative lengthening of telomeres (ALT) mechanism or with a non-defined telomere maintenance mechanism (NDTMM), using immunohistochemistry and quantitative PCR. We also tested the affect of PAX8 knockdown using siRNA in cell lines on cell survival and BCL2 expression.Results:Seventy-two percent of glioblastomas were PAX8-positive (80% telomerase, 73% NDTMM, and 44% ALT). The majority of the low-grade gliomas and normal brain cells were PAX8-negative. The suppression of PAX8 was associated with a reduction in both cell growth and BCL2, suggesting that a reduction in PAX8 expression would sensitise tumours to cell death.Conclusions:PAX8 is increased in the majority of glioblastomas and promoted cell survival. Because PAX8 is absent in normal brain tissue, it may be a promising therapeutic target pathway for treating aggressive gliomas.
Keyword
- PAX8
- Glioblastoma
- Glioma
- Telomere maintenance mechanism
- Telomerase
- ALT
- BCL2
- Cell survival
Publication and Content Type
- ref (subject category)
- art (subject category)
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BMC Cancer
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- By the author/editor
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Hung, Noelyn
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Chen, Yu-Jen
-
Taha, Ahmad
-
Olivecrona, Magn ...
-
Boet, Ronald
-
Wiles, Anna
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show more...
-
Warr, Tracy
-
Shaw, Alisha
-
Eiholzer, Ramona
-
Baguley, Bruce C ...
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Eccles, Michael ...
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Braithwaite, Ant ...
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MacFarlane, Mart ...
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Royds, Janice A.
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Slatter, Tania
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show less...
- Articles in the publication
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BMC Cancer
- By the university
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Umeå University