Document Detail

Gli1 inhibition induces cell-cycle arrest and enhanced apoptosis in brain glioma cell lines.
MedLine Citation:
PMID:  20024601     Owner:  NLM     Status:  MEDLINE    
The Hedgehog (HH)-Gli1 signaling pathway plays an important role in the patterning and development of the central nervous system during embryogenesis. Recent data have shown its possible involvement in a subset of human gliomas, and inhibition of the pathway resulted in tumor suppression in both in vitro and in vivo studies. The underlying mechanisms of tumor suppression, however, remain to be fully elucidated. Here, we investigated Gli1 expression in 65 surgically resected malignant glioma tissues and found the Ki-67 labeling index to be higher in Gli1-positive gliomas than in Gli1-negative gliomas. Depletion of Gli1 expression by small interfering RNA (siRNA) interference led to remarkably decreased cell proliferation and enhanced apoptosis in U87 glioma cell line. To explore the molecular mechanisms of the phenotypic changes, we performed real-time quantitative RT-PCR analysis to monitor the changes of a series of genes which play critical roles in the regulation of cell cycle and apoptosis. The result showed that downregulation of G(1) cyclins, downregulation of Bcl-2, and upregulation of p21 were detected after Gli1 downregulation. Additionally, cyclopamine was used to inhibit the HH signaling activity as an indirect approach to decrease Gli1 expression, and we observed that cyclopamine exclusively inhibited cell growth in HH-pathway-active glioma cell lines. The cell phenotypic and molecular changes induced by cyclopamine were consistent with those caused by siGli1 interference. In conclusion, our findings support an important role of Gli1 in cell-cycle and apoptosis regulation in human brain gliomas; hence, it can serve as a potential target of new therapeutic strategies for these diseases.
Ke Wang; Li Pan; Xiaoming Che; Daming Cui; Chao Li
Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2009-12-19
Journal Detail:
Title:  Journal of neuro-oncology     Volume:  98     ISSN:  1573-7373     ISO Abbreviation:  J. Neurooncol.     Publication Date:  2010 Jul 
Date Detail:
Created Date:  2010-06-14     Completed Date:  2010-09-17     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  8309335     Medline TA:  J Neurooncol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  319-27     Citation Subset:  IM    
Department of Neurosurgery, Huashan Hospital, Fudan University, Shanghai 200040, China.
Export Citation:
APA/MLA Format     Download EndNote     Download BibTex
MeSH Terms
Apoptosis / drug effects*,  genetics
Brain Neoplasms / physiopathology*
Cell Cycle / drug effects*,  genetics
Cell Line, Tumor
Cell Proliferation / drug effects
Dose-Response Relationship, Drug
Down-Regulation / drug effects,  physiology*
Flow Cytometry
Glioma / physiopathology*
Ki-67 Antigen / metabolism
Oncogene Proteins / metabolism*
RNA Interference / physiology
RNA, Small Interfering / pharmacology
Signal Transduction / drug effects
Time Factors
Trans-Activators / metabolism*
Transfection / methods
Veratrum Alkaloids / pharmacology
Reg. No./Substance:
0/Gli protein; 0/Ki-67 Antigen; 0/Oncogene Proteins; 0/RNA, Small Interfering; 0/Trans-Activators; 0/Veratrum Alkaloids; 4449-51-8/cyclopamine

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

Previous Document:  Microarray analysis of p-anisaldehyde-induced transcriptome of Saccharomyces cerevisiae.
Next Document:  Robust structure-based resonance assignment for functional protein studies by NMR.