PMID- 21572341
OWN - NLM
STAT- MEDLINE
DCOM- 20110722
LR  - 20171116
IS  - 1554-6578 (Electronic)
IS  - 0022-3069 (Linking)
VI  - 70
IP  - 6
DP  - 2011 Jun
TI  - GLI2 is a potential therapeutic target in pediatric medulloblastoma.
PG  - 430-7
LID - 10.1097/NEN.0b013e31821b94db [doi]
AB  - To determine whether the zinc finger transcription factors GLI1 to GLI3 and 
      suppressor of fused (SUFU) components of the Sonic hedgehog signaling pathway may 
      be prognostic markers and potential therapeutic targets in pediatric 
      medulloblastoma (MB), we investigated the relationship of the expression of these 
      proteins to prognosis in the MB of 124 patients who had undergone surgery at the 
      Hospital for Sick Children (Toronto, Ontario, Canada). The expressions of GLI1 (p 
      = 0.011) and GLI2 (p = 0.003), but not of GLI3 (p = 0.774) or SUFU (p = 0.137), 
      in the MB were associated with a worse overall survival by Kaplan-Meier analysis. 
      Overall survival of patients positive for GLI1 and GLI2 was 6.01 +/- 0.85 years and 
      5.27 +/- 1.44 years, respectively, versus 10.11 +/- 1.52 years and 10.18 +/- 0.22 years 
      for patients negative for GLI1 and GLI2, respectively. Knockdown of GLI2 in 3 MB 
      cell lines resulted in decreased cell number and viability, as determined by the 
      MTT (3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assay; 
      knockdown of GLI1 had no effect. The decrease in cell number with GLI2 knockdown 
      was caused by G0 cell cycle arrest; there was no induction of apoptosis. These 
      results suggest that targeting the Sonic hedgehog pathway in positive patients 
      may be a useful adjuvant therapeutic strategy for MB.
FAU - Buczkowicz, Pawel
AU  - Buczkowicz P
AD  - Division of Pathology, Department of Paediatric Laboratory Medicine, The Hospital 
      for Sick Children, University of Toronto, Canada.
FAU - Ma, Jing
AU  - Ma J
FAU - Hawkins, Cynthia
AU  - Hawkins C
LA  - eng
GR  - MOP 82727/Canadian Institutes of Health Research/Canada
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - England
TA  - J Neuropathol Exp Neurol
JT  - Journal of neuropathology and experimental neurology
JID - 2985192R
RN  - 0 (GLI1 protein, human)
RN  - 0 (GLI2 protein, human)
RN  - 0 (Kruppel-Like Transcription Factors)
RN  - 0 (Nuclear Proteins)
RN  - 0 (RNA, Small Interfering)
RN  - 0 (Transcription Factors)
RN  - 0 (Zinc Finger Protein GLI1)
RN  - 0 (Zinc Finger Protein Gli2)
SB  - IM
MH  - Adolescent
MH  - Apoptosis/drug effects/*physiology
MH  - Cell Line, Tumor
MH  - Cerebellar Neoplasms/*metabolism/pathology
MH  - Child
MH  - Child, Preschool
MH  - Female
MH  - Gene Expression Regulation/drug effects/genetics
MH  - Humans
MH  - In Situ Nick-End Labeling/methods
MH  - Infant
MH  - Kruppel-Like Transcription Factors/genetics/*metabolism
MH  - Male
MH  - Medulloblastoma/*metabolism/pathology
MH  - Nuclear Proteins/genetics/*metabolism
MH  - Pediatrics
MH  - RNA, Small Interfering/pharmacology
MH  - Retrospective Studies
MH  - Transcription Factors/genetics/metabolism
MH  - Transduction, Genetic/methods
MH  - Zinc Finger Protein GLI1
MH  - Zinc Finger Protein Gli2
EDAT- 2011/05/17 06:00
MHDA- 2011/07/23 06:00
CRDT- 2011/05/17 06:00
PHST- 2011/05/17 06:00 [entrez]
PHST- 2011/05/17 06:00 [pubmed]
PHST- 2011/07/23 06:00 [medline]
AID - 10.1097/NEN.0b013e31821b94db [doi]
PST - ppublish
SO  - J Neuropathol Exp Neurol. 2011 Jun;70(6):430-7. doi: 
      10.1097/NEN.0b013e31821b94db.