Giant cell glioblastoma is associated with altered aurora b expression and concomitant p53 mutation.
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Giant cell glioblastoma is associated with altered aurora b expression and concomitant p53 mutation. / Temme, Achim; Geiger, Kathrin D; Wiedemuth, Ralf; Conseur, Katharina; Pietsch, Torsten; Felsberg, Jörg; Reifenberger, Guido; Tatsuka, Masaaki; Hagel, Christian; Westphal, Manfred; Berger, Hilmar; Simon, Matthias; Weller, Michael; Schackert, Gabriele.
in: J NEUROPATH EXP NEUR, Jahrgang 69, Nr. 6, 6, 2010, S. 632-642.Publikationen: SCORING: Beitrag in Fachzeitschrift/Zeitung › SCORING: Zeitschriftenaufsatz › Forschung › Begutachtung
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TY - JOUR
T1 - Giant cell glioblastoma is associated with altered aurora b expression and concomitant p53 mutation.
AU - Temme, Achim
AU - Geiger, Kathrin D
AU - Wiedemuth, Ralf
AU - Conseur, Katharina
AU - Pietsch, Torsten
AU - Felsberg, Jörg
AU - Reifenberger, Guido
AU - Tatsuka, Masaaki
AU - Hagel, Christian
AU - Westphal, Manfred
AU - Berger, Hilmar
AU - Simon, Matthias
AU - Weller, Michael
AU - Schackert, Gabriele
PY - 2010
Y1 - 2010
N2 - Giant cell glioblastoma (gcGB), a subtype of GB, is characterized by the presence of numerous multinucleated giant cells. The prognosis for gcGB is poor, but it may have a better clinical outcome compared with classic GB. The molecular alterations that lead to the multinucleated cell phenotype of gcGB have not been elucidated. Giant cell GB has a higher frequency of the tumor suppressor protein p53 mutations than GB, however, and a role for the mitotic Aurora B kinase has been suggested. We analyzed Aurora B expression in gcGB (n = 28) and GB (n = 54) patient tumor samples by immunohistochemistry; 17 gcGB and 22 GB samples were analyzed at the DNA and mRNA levels. No mutations in the Aurora B gene (AURKB) were found, but its mRNA and protein levels were significantly higher in gcGB than in GB. Fifty-nine percent of gcGB samples but only 18% of the GB samples showed p53 mutations. Ectopic overexpression of Aurora B induced a significant increase inthe proportion of multinucleated cells in p53 mutant U373-MG, but not in p53 wild-type U87-MG, glioma cells. RNAi of p53 in U87-MG cells led to an increase in the fraction of multinucleated cells that was further augmented by ectopic overexpression of Aurora B. These results suggest that loss of p53 function and dysregulated Aurora B protein levels might represent factors that drive the development of multinucleated cells in gcGB.
AB - Giant cell glioblastoma (gcGB), a subtype of GB, is characterized by the presence of numerous multinucleated giant cells. The prognosis for gcGB is poor, but it may have a better clinical outcome compared with classic GB. The molecular alterations that lead to the multinucleated cell phenotype of gcGB have not been elucidated. Giant cell GB has a higher frequency of the tumor suppressor protein p53 mutations than GB, however, and a role for the mitotic Aurora B kinase has been suggested. We analyzed Aurora B expression in gcGB (n = 28) and GB (n = 54) patient tumor samples by immunohistochemistry; 17 gcGB and 22 GB samples were analyzed at the DNA and mRNA levels. No mutations in the Aurora B gene (AURKB) were found, but its mRNA and protein levels were significantly higher in gcGB than in GB. Fifty-nine percent of gcGB samples but only 18% of the GB samples showed p53 mutations. Ectopic overexpression of Aurora B induced a significant increase inthe proportion of multinucleated cells in p53 mutant U373-MG, but not in p53 wild-type U87-MG, glioma cells. RNAi of p53 in U87-MG cells led to an increase in the fraction of multinucleated cells that was further augmented by ectopic overexpression of Aurora B. These results suggest that loss of p53 function and dysregulated Aurora B protein levels might represent factors that drive the development of multinucleated cells in gcGB.
M3 - SCORING: Zeitschriftenaufsatz
VL - 69
SP - 632
EP - 642
JO - J NEUROPATH EXP NEUR
JF - J NEUROPATH EXP NEUR
SN - 0022-3069
IS - 6
M1 - 6
ER -
