DEK proto-oncogene is highly expressed in astrocytic tumors and regulates glioblastoma cell proliferation and apoptosis

被引:18
作者
Feng, Tianda [1 ]
Liu, Yunhui [1 ]
Li, Chao [2 ]
Li, Zhen [1 ]
Cai, Heng [1 ]
机构
[1] China Med Univ, Shengjing Hosp, Dept Neurosurg, 36 Sanhao St, Shenyang 110004, Liaoning, Peoples R China
[2] Zhejiang Chinese Med Univ, Guangxing Hosp, Dept Neurosurg, Hangzhou, Zhejiang, Peoples R China
关键词
Astrocytic tumor; DEK; small interfering RNA; proliferation; apoptosis; ONCOPROTEIN; AUTOANTIBODIES; CHROMATIN; TOPOLOGY; THERAPY;
D O I
10.1177/1010428317716248
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
Astrocytic tumors are the most common neuroepithelial neoplasms with high relapse rate after surgery. Understanding the molecular mechanisms for astrocytic tumorigenesis and progression will lead to early diagnosis and effective treatment of astrocytic tumors. The DEK mRNA and protein expression in normal brain tissues and astrocytic tumors was quantified. To investigate DEK functions in tumor cells, DEK gene was silenced with siRNA in U251 glioblastoma cells. Cell proliferation, cell cycle and apoptosis were then measured. The expression and activity of key genes that regulate cell proliferation and apoptosis were also measured. We identified DEK as a high expressed gene in astrocytic tumor tissues. DEK expression level was positively correlated with the pathological grade of astrocytic tumors. Gene silencing of DEK in U251 glioblastomas inhibited cell proliferation and blocked cells at G0/G1 phase of cell cycle. DEK depletion also induced cell apoptosis, with up-regulated expression of P53 and P21 and down-regulated expression of Bcl-2 and C-myc. The Caspase-3 activity in U251 cells was also significantly increased after knockdown. Our results provided evidences that DEK regulates proliferation and apoptosis of glioblastomas. DEK gene silencing may induce apoptosis through P53-dependent pathway. Our data indicated DEK plays multiple roles to facilitate tumor growth and maintenance. It can be used as a potential target for astrocytic tumor diagnosis and gene therapy.
引用
收藏
页码:1 / 10
页数:10
相关论文
共 33 条
[1]  
Alexiadis V, 2000, GENE DEV, V14, P1308
[2]   DEK expression is controlled by E2F and deregulated in diverse tumor types [J].
Carro, Maria Stella ;
Spiga, Fabio Mario ;
Quarto, Micaela ;
Di Ninni, Valentina ;
Volorio, Sara ;
Alcalay, Myriam ;
Muller, Heiko .
CELL CYCLE, 2006, 5 (11) :1202-1207
[3]   Hypoxia in astrocytic tumors and implications for therapy [J].
Cavazos, David A. ;
Brenner, Andrew J. .
NEUROBIOLOGY OF DISEASE, 2016, 85 :227-233
[4]   Survival rates and patterns of care for patients diagnosed with supratentorial low-grade gliomas - Data from the SEER program, 1973-2001 [J].
Claus, EB ;
Black, PM .
CANCER, 2006, 106 (06) :1358-1363
[5]  
Dong XW, 1998, ARTHRITIS RHEUM-US, V41, P1505, DOI 10.1002/1529-0131(199808)41:8<1505::AID-ART23>3.0.CO
[6]  
2-N
[7]  
Dong XW, 2000, ARTHRITIS RHEUM-US, V43, P85, DOI 10.1002/1529-0131(200001)43:1<85::AID-ANR11>3.0.CO
[8]  
2-D
[9]   Malignant astrocytic glioma: genetics, biology, and paths to treatment [J].
Furnari, Frank B. ;
Fenton, Tim ;
Bachoo, Robert M. ;
Mukasa, Akitake ;
Stommel, Jayne M. ;
Stegh, Alexander ;
Hahn, William C. ;
Ligon, Keith L. ;
Louis, David N. ;
Brennan, Cameron ;
Chin, Lynda ;
DePinho, Ronald A. ;
Cavenee, Webster K. .
GENES & DEVELOPMENT, 2007, 21 (21) :2683-2710
[10]   DEK-CAN molecular monitoring of myeloid malignancies could aid therapeutic stratification [J].
Garçon, L ;
Libura, M ;
Delabesse, E ;
Valensi, F ;
Asnafi, V ;
Berger, C ;
Schmitt, C ;
Leblanc, T ;
Buzyn, A ;
Macintyre, E .
LEUKEMIA, 2005, 19 (08) :1338-1344