Human positive coactivator 4 (PC4) is involved in the progression and prognosis of astrocytoma

被引:18
作者
Chen, Lei [1 ]
Du, Cheng [2 ]
Wang, Liang [1 ]
Yang, Chen [1 ]
Zhang, Jia-rui [3 ]
Li, Nan [1 ]
Li, Yi [1 ]
Xie, Xiao-dong [2 ]
Gao, Guo-dong [1 ]
机构
[1] Fourth Mil Med Univ, TangDu Hosp, Dept Neurosurg, Xian 710038, Shaanxi, Peoples R China
[2] Gen Hosp Shenyang Mil Reg, Dept Oncol, Shenyang 110016, Peoples R China
[3] Fourth Mil Med Univ, TangDu Hosp, Dept Pathol, Xian 710038, Shaanxi, Peoples R China
关键词
Human transcriptional coactivator 4; Astrocytoma; Clinicopathology; Tumorigenesis; Tumor progression; Survival; GENE-EXPRESSION; BRAIN-TUMORS; P53; FUNCTION; DNA; GLIOBLASTOMA; RADIOTHERAPY; ACTIVATION; PROTEIN; GLIOMAS; TARGET;
D O I
10.1016/j.jns.2014.09.014
中图分类号
R74 [神经病学与精神病学];
学科分类号
摘要
Astrocytoma is the most common primary brain tumor and it is associated with poor prognosis. Accumulating evidences suggest that certain molecular abnormalities or genetic mutations are associated with its progression and prognosis. Human transcriptional coactivator 4 (PC4), originally identified as a transcriptional coactivator then as a DNA replication and repair factor has been shown to be involved in chromatin organization. Recently, it is reported to function both as tumor suppressor and promoter depending on the cellular settings. In the present study, we for the first time demonstrated that the expression of PC4 in astrocytoma was upregulated as assessed by western blot and immunohistochemical staining. Moreover, elevated PC4 expression was strongly correlated with the progression of astrocytoma. Furthermore, high PC4 expression was also associated with poor overall survival. Finally, in vitro study demonstrated that siRNA mediated PC4 downregulation significantly inhibited the proliferation and invasiveness of human glioma cells. These results suggested that PC4 might play a role in human astrocytoma progression and may be used as a novel indicator for the prognosis of astrocytoma patient. (C) 2014 Elsevier B.V. All rights reserved.
引用
收藏
页码:293 / 298
页数:6
相关论文
共 25 条
[1]   General transcriptional coactivator PC4 activates p53 function [J].
Banerjee, S ;
Kumar, BRP ;
Kundu, TK .
MOLECULAR AND CELLULAR BIOLOGY, 2004, 24 (05) :2052-2062
[2]   Activation of p53 function by human transcriptional coactivator PC4: Role of protein-protein interaction, DNA bending, and Posttranslational modifications [J].
Batta, Kiran ;
Kundu, Tapas K. .
MOLECULAR AND CELLULAR BIOLOGY, 2007, 27 (21) :7603-7614
[3]   Human Transcriptional Coactivator PC4 Stimulates DNA End Joining and Activates DSB Repair Activity [J].
Batta, Kiran ;
Yokokawa, Masatoshi ;
Takeyasu, Kunio ;
Kundu, Tapas K. .
JOURNAL OF MOLECULAR BIOLOGY, 2009, 385 (03) :788-799
[4]   Comprehensive genomic characterization defines human glioblastoma genes and core pathways [J].
Chin, L. ;
Meyerson, M. ;
Aldape, K. ;
Bigner, D. ;
Mikkelsen, T. ;
VandenBerg, S. ;
Kahn, A. ;
Penny, R. ;
Ferguson, M. L. ;
Gerhard, D. S. ;
Getz, G. ;
Brennan, C. ;
Taylor, B. S. ;
Winckler, W. ;
Park, P. ;
Ladanyi, M. ;
Hoadley, K. A. ;
Verhaak, R. G. W. ;
Hayes, D. N. ;
Spellman, Paul T. ;
Absher, D. ;
Weir, B. A. ;
Ding, L. ;
Wheeler, D. ;
Lawrence, M. S. ;
Cibulskis, K. ;
Mardis, E. ;
Zhang, Jinghui ;
Wilson, R. K. ;
Donehower, L. ;
Wheeler, D. A. ;
Purdom, E. ;
Wallis, J. ;
Laird, P. W. ;
Herman, J. G. ;
Schuebel, K. E. ;
Weisenberger, D. J. ;
Baylin, S. B. ;
Schultz, N. ;
Yao, Jun ;
Wiedemeyer, R. ;
Weinstein, J. ;
Sander, C. ;
Gibbs, R. A. ;
Gray, J. ;
Kucherlapati, R. ;
Lander, E. S. ;
Myers, R. M. ;
Perou, C. M. ;
McLendon, Roger .
NATURE, 2008, 455 (7216) :1061-1068
[5]   Transcriptional coactivator PC4, a chromatin-associated protein, induces chromatin condensation [J].
Das, Chandrima ;
Hizume, Kohji ;
Batta, Kiran ;
Kumar, B. R. Prashanth ;
Gadad, Shrikanth S. ;
Ganguly, Semanti ;
Lorain, Stephanie ;
Verreault, Alain ;
Sadhale, Parag P. ;
Takeyasu, Kunio ;
Kundu, Tapas K. .
MOLECULAR AND CELLULAR BIOLOGY, 2006, 26 (22) :8303-8315
[6]   Human Positive Coactivator 4 Controls Heterochromatinization and Silencing of Neural Gene Expression by Interacting with REST/NRSF and CoREST [J].
Das, Chandrima ;
Gadad, Shrikanth S. ;
Kundu, Tapas K. .
JOURNAL OF MOLECULAR BIOLOGY, 2010, 397 (01) :1-12
[7]   Augmentation of tumor angiogenesis by a Myc-activated microRNA cluster [J].
Dews, Michael ;
Homayouni, Asal ;
Yu, Duonan ;
Murphy, Danielle ;
Sevignani, Cinzia ;
Wentzel, Erik ;
Furth, Emma E. ;
Lee, William M. ;
Enders, Greg H. ;
T Mendell, Joshua ;
Thomas-Tikhonenko, Andrei .
NATURE GENETICS, 2006, 38 (09) :1060-1065
[8]   Genetic causes of brain tumors: Neurofibromatosis, tuberous sclerosis, von Hippel-Lindau, and other syndromes [J].
Farrell, Christopher J. ;
Plotkin, Scott R. .
NEUROLOGIC CLINICS, 2007, 25 (04) :925-+
[9]   Estrogen Receptor, Progesterone Receptor, Human Epidermal Growth Factor Receptor 2 (HER2), and Epidermal Growth Factor Receptor Expression and Benefit From Lapatinib in a Randomized Trial of Paclitaxel With Lapatinib or Placebo As First-Line Treatment in HER2-Negative or Unknown Metastatic Breast Cancer [J].
Finn, Richard S. ;
Press, Michael F. ;
Dering, Judy ;
Arbushites, Michael ;
Koehler, Maria ;
Oliva, Cristina ;
Williams, Lisa S. ;
Di Leo, Angelo .
JOURNAL OF CLINICAL ONCOLOGY, 2009, 27 (24) :3908-3915
[10]   Epidemiology of brain tumors [J].
Fisher, James L. ;
Schwartzbaum, Judith A. ;
Wrensch, Margaret ;
Wiemels, Joseph L. .
NEUROLOGIC CLINICS, 2007, 25 (04) :867-+