title: Increased paired box transcription factor 8 has a survival function in glioma.
abstract: 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.
authors.forename: Noelyn
authors.initials: N
authors.lastname: Hung
authors.forename: Yu-Jen
authors.initials: YJ
authors.lastname: Chen
authors.forename: Ahmad
authors.initials: A
authors.lastname: Taha
authors.forename: Magnus
authors.initials: M
authors.lastname: Olivecrona
authors.forename: Ronald
authors.initials: R
authors.lastname: Boet
authors.forename: Anna
authors.initials: A
authors.lastname: Wiles
authors.forename: Tracy
authors.initials: T
authors.lastname: Warr
authors.forename: Alisha
authors.initials: A
authors.lastname: Shaw
authors.forename: Ramona
authors.initials: R
authors.lastname: Eiholzer
authors.forename: Bruce C
authors.initials: BC
authors.lastname: Baguley
authors.forename: Michael R
authors.initials: MR
authors.lastname: Eccles
authors.forename: Antony W
authors.initials: AW
authors.lastname: Braithwaite
authors.forename: Martin
authors.initials: M
authors.lastname: Macfarlane
authors.forename: Janice A
authors.initials: JA
authors.lastname: Royds
authors.affiliation: Department of Pathology, University of Otago, Dunedin, New Zealand. tania.slatter@otago.ac.nz.
authors.forename: Tania
authors.initials: T
authors.lastname: Slatter
mesh_terms: D049109:Cell Proliferation; D002470:Cell Survival; D015870:Gene Expression; D020868:Gene Silencing; D005910:Glioma / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D007150:Immunohistochemistry; D051757:PAX5 Transcription Factor / Q000378:metabolism; D000072636:PAX8 Transcription Factor; D051761:Paired Box Transcription Factors / Q000235:genetics / Q000378:metabolism*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics / Q000378:metabolism; D034741:RNA, Small Interfering / Q000235:genetics
chemical_list: D051757:PAX5 Transcription Factor; C497281:PAX5 protein, human; D000072636:PAX8 Transcription Factor; C083325:PAX8 protein, human; D051761:Paired Box Transcription Factors; D019253:Proto-Oncogene Proteins c-bcl-2; D034741:RNA, Small Interfering