Differential expression of centrosomal proteins at different stages of human glioma.
BACKGROUND
High-grade gliomas have poor prognosis, requiring aggressive treatment. The aim of this study is to explore mitotic and centrosomal dysregulation in gliomas, which may provide novel targets for treatment.


METHODS
A case-control study was performed using 34 resected gliomas, which were separated into low- and high-grade groups. Normal human brain tissue was used as a control. Using immunohistochemical analysis, immunofluorescent microscopy, and RT-PCR, detection of centrins 1 and 2, gamma-tubulin, hNinein, Aurora A, and Aurora B, expression was performed. Analysis of the GBM8401 glioma cell line was also undertaken to complement the in vivo studies.


RESULTS
In high-grade gliomas, the cells had greater than two very brightly staining centrioles within large, atypical nuclei, and moderate-to-strong Aurora A staining. Comparing with normal human brain tissue, most of the mRNAs expression in gliomas for centrosomal structural proteins, including centrin 3, gamma-tubulin, and hNinein isoforms 1, 2, 5 and 6, Aurora A and Aurora B were elevated. The significant different expression was observed between high- and low-grade glioma in both gamma-tubulin and Aurora A mRNA s. In the high-grade glioma group, 78.6% of the samples had higher than normal expression of gamma-tubulin mRNA, which was significantly higher than in the low-grade glioma group (18.2%, p < 0.05).


CONCLUSIONS
Markers for mitotic dysregulation, such as supernumerary centrosomes and altered expression of centrosome-related mRNA and proteins were more frequently detected in higher grade gliomas. Therefore, these results are clinically useful for glioma staging as well as the development of novel treatments strategies.
Loh
Joon-Khim
JK
Department of Neurosurgery, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan.
Lieu
Ann-Shung
AS
Chou
Chia-Hua
CH
Lin
Fang-Yi
FY
Wu
Chia-Hung
CH
Howng
Sheng-Long
SL
Chio
Chung-Ching
CC
Hong
Yi-Ren
YR
D000328:Adult; D000368:Aged; D001932:Brain Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D016022:Case-Control Studies; D018797:Cell Cycle Proteins / Q000235:genetics / Q000378:metabolism*; D045744:Cell Line, Tumor; D018385:Centrosome / Q000378:metabolism*; D015972:Gene Expression Regulation, Neoplastic; D005910:Glioma / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008856:Microscopy, Fluorescence; D008868:Microtubule Proteins / Q000235:genetics / Q000378:metabolism*; D008875:Middle Aged; D008938:Mitosis; D009367:Neoplasm Staging; D012333:RNA, Messenger / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction
D018797:Cell Cycle Proteins; D008868:Microtubule Proteins; D012333:RNA, Messenger