Glycinamide ribonucleotide formyl transferase is frequently overexpressed in glioma and critically regulates the proliferation of glioma cells.
OBJECTIVE
Current treatments for the most common form of brain tumor, glioma, are disappointing in their effectiveness. Low expression levels of GART, an enzyme in the core nucleotide metabolism, significantly correlate with chemosensitivity, conferring a survival advantage to tumor cells. Our study aimed to explore the expression and function of GART in glioma.


METHODS
Immunohistochemical and Western blot analysis were performed in 70 cases of human gliomas and normal brain tissues. We mainly used cell growth assay and multicellular tumor spheroid formation assay to evaluate the proliferation and chemosensitivity of glioma cells.


RESULTS
High GART expression (most cancer cells cytoplasm stained) was observed in 70 specimens and was related to the grade of malignancy. We also reviewed each grade of tumors separately and investigated whether GART expression predicted patient survival within each subgroup. In brief, GART overexpression was significantly associated with overall survival (P=0.03). Interestingly, transfecting cells with GART-siRNA suppressed proliferation and enhanced temozolomide (TMZ)-induced apoptosis in glioma cells.


CONCLUSIONS
The current results showed that GART expression was associated with glioma grade and that high GART protein expression might be related to poor outcome.
Department of Radiation Oncology, Affiliated Hospital of Nantong University, Nantong, Jiangsu, China.
Xiancheng
X
Liu
Department of Pathology, Medical College, Nantong University, Nantong, Jiangsu, China.
Zongmei
Z
Ding
Department of Immunology and Microbiology, Medical College of Nantong University, Nantong, Jiangsu, China.
Yonghua
Y
Liu
Department of Radiation Oncology, Affiliated Hospital of Nantong University, Nantong, Jiangsu, China.
Jianguo
J
Zhang
Department of Pathology, Medical College, Nantong University, Nantong, Jiangsu, China.
Fang
F
Liu
Department of Immunology and Microbiology, Medical College of Nantong University, Nantong, Jiangsu, China.
Xinxiu
X
Wang
Department of Pathology, Medical College, Nantong University, Nantong, Jiangsu, China.
Xiaojuan
X
He
Department of Neurosurgery, The First Affiliated Hospital of Soochow University, Suzhou, Jiangsu, China. Electronic address: cuigang33@sina.cn.
Gang
G
Cui
Department of Pathology, Medical College, Nantong University, Nantong, Jiangsu, China. Electronic address: meimei19871001@sina.com.
Donglin
D
Wang
D000328:Adult; D014408:Biomarkers, Tumor; D015153:Blotting, Western; D001932:Brain Neoplasms / Q000201:enzymology* / Q000401:mortality / Q000473:pathology*; D019731:Carbon-Nitrogen Ligases / Q000032:analysis / Q000096:biosynthesis*; D049109:Cell Proliferation; D005260:Female; D005910:Glioma / Q000201:enzymology* / Q000401:mortality / Q000473:pathology*; D006801:Humans; D007150:Immunohistochemistry; D053208:Kaplan-Meier Estimate; D008297:Male; D051026:Phosphoribosylglycinamide Formyltransferase / Q000032:analysis / Q000096:biosynthesis*; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction
D014408:Biomarkers, Tumor; D051026:Phosphoribosylglycinamide Formyltransferase; D019731:Carbon-Nitrogen Ligases; C494823:GART protein, human
GART; Glioma; Proliferation; TMZ