Open Access Research article

Increased paired box transcription factor 8 has a survival function in Glioma

Noelyn Hung1, Yu-Jen Chen1, Ahmad Taha2, Magnus Olivecrona3, Ronald Boet4, Anna Wiles5, Tracy Warr6, Alisha Shaw1, Ramona Eiholzer1, Bruce C Baguley7, Michael R Eccles1, Antony W Braithwaite18, Martin MacFarlane4, Janice A Royds1 and Tania Slatter1*

Author Affiliations

1 Department of Pathology, University of Otago, Dunedin, New Zealand

2 Dunedin Public Hospital, Dunedin, New Zealand

3 Department of Pharmacology and Clinical Neuroscience, Neurosurgery, Umea University, Umea, Sweden

4 Christchurch Hospital, Christchurch, New Zealand

5 Department of Medicine, Dunedin School of Medicine, University of Otago, Dunedin, New Zealand

6 Department of Molecular Neuroscience, Institute of Neurology, National Hospital for Neurology and Neurosurgery, London, UK

7 Auckland Cancer Society Research Centre, Faculty of Medical and Health Sciences, University of Auckland, Auckland, New Zealand

8 Children’s medical research Institute, University of Sydney, Westmead, Australia

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BMC Cancer 2014, 14:159  doi:10.1186/1471-2407-14-159

Published: 6 March 2014



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.


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.


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.


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.

PAX8; Glioblastoma; Glioma; Telomere maintenance mechanism; Telomerase; ALT; BCL2; Cell survival