Blockade of SOX4 mediated DNA repair by SPARC enhances radioresponse in medulloblastoma

被引:22
作者
Chetty, Chandramu [1 ]
Dontula, Ranadheer [4 ]
Gujrati, Meena [2 ]
Dinh, Dzung H. [3 ]
Lakka, Sajani S. [4 ]
机构
[1] Univ Illinois, Coll Med Peoria, Dept Canc Biol & Pharmacol, Peoria, IL 61605 USA
[2] Univ Illinois, Coll Med Peoria, Dept Pathol, Peoria, IL 61605 USA
[3] Univ Illinois, Coll Med Peoria, Dept Neurosurg, Peoria, IL 61605 USA
[4] Univ Illinois, Coll Med Chicago, Dept Med, Sect Hematol & Oncol MC713, Chicago, IL 60612 USA
关键词
SPARC; SOX4; Medulloblastoma; Radiosensitization; CANCER-CELLS; DIFFERENTIAL EXPRESSION; MITOTIC CATASTROPHE; TUMOR-CELLS; NULL MICE; APOPTOSIS; DAMAGE; RADIATION; PROTEIN; GENES;
D O I
10.1016/j.canlet.2012.04.014
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
SPARC is a matricellular glycoprotein and a putative radioresistance-reversal-gene. We therefore explored the possibility of SPARC expression on medulloblastoma radiosensitivity in vitro and in vivo. The combined treatment of the SPARC and irradiation resulted in increased cell death when compared to cells treated with irradiation alone in vitro and in vivo. SPARC expression prior to irradiation suppressed checkpoints-1,-2 and p53 phosphorylation and DNA repair gene XRCC1. We also demonstrate that SPARC expression suppressed irradiation induced SOX-4 mediated DNA repair. These results provide evidence of the anti-tumor effect of combining SPARC with irradiation as a new therapeutic strategy for the treatment of medulloblastoma. (c) 2012 Elsevier Ireland Ltd. All rights reserved.
引用
收藏
页码:188 / 198
页数:11
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