Glycogen synthase kinase-3beta regulates astrocytic differentiation of U87-MG human glioblastoma cells.
OBJECTIVE
To evaluate the role of glycogen synthase kinase-3beta (GSK-3beta) in the induced differentiation of human glioblastoma cells.


METHODS
Cell proliferation was determined by bromodeoxyuridine (BrdU) incorporation assay. The protein level of p-GSK-3beta, GSK-3beta, glial fibrillary acidic protein (GFAP) and proliferating cell nuclear antigen (PCNA) were determined using Western blots. The overexpression of mutant GSK-3beta was analyzed by immunocytochemistry.


RESULTS
The biotoxin cholera toxin is capable of inducing differentiation of U87-MG human glioblastoma cells, which is characterized by morphological changes to astrocytic phenotype, increase in differentiation marker protein GFAP and decrease in proliferation. GSK-3beta activation is induced during this differentiation. Small interfering RNA against GSK-3beta suppresses the induced-differentiation in U87-MG cells. Conversely, overexpression of a constitutively active form of human GSK-3beta (pcDNA3-GSK-3beta-S9A) mutant leads to differentiation of U87-MG cells.


CONCLUSIONS
Our findings suggest that GSK-3beta plays an important role in astrocytic differentiation of human glioblastoma cells and may be a novel therapeutic target in the malignant tumor.
Department of Infectious Diseases, Third Affiliated Hospital of Sun Yat-Sen University, Guangzhou, China.
Yan
Y
Li
Hui-min
HM
Lu
Gang
G
Li
Guang-mei
GM
Yan
D001253:Astrocytes / Q000166:cytology*; D002454:Cell Differentiation / Q000187:drug effects; D045744:Cell Line, Tumor; D002772:Cholera Toxin / Q000494:pharmacology; D015972:Gene Expression Regulation, Neoplastic; D005909:Glioblastoma / Q000201:enzymology*; D038362:Glycogen Synthase Kinase 3 / Q000235:genetics / Q000378:metabolism*; D000071679:Glycogen Synthase Kinase 3 beta; D006801:Humans
D002772:Cholera Toxin; C000605506:GSK3B protein, human; D000071679:Glycogen Synthase Kinase 3 beta; D038362:Glycogen Synthase Kinase 3