RRC ID 35684
Author Murakami-Tonami Y, Kishida S, Takeuchi I, Katou Y, Maris JM, Ichikawa H, Kondo Y, Sekido Y, Shirahige K, Murakami H, Kadomatsu K.
Title Inactivation of SMC2 shows a synergistic lethal response in MYCN-amplified neuroblastoma cells.
Journal Cell Cycle
Abstract The condensin complex is required for chromosome condensation during mitosis; however, the role of this complex during interphase is unclear. Neuroblastoma is the most common extracranial solid tumor of childhood, and it is often lethal. In human neuroblastoma, MYCN gene amplification is correlated with poor prognosis. This study demonstrates that the gene encoding the condensin complex subunit SMC2 is transcriptionally regulated by MYCN. SMC2 also transcriptionally regulates DNA damage response genes in cooperation with MYCN. Downregulation of SMC2 induced DNA damage and showed a synergistic lethal response in MYCN-amplified/overexpression cells, leading to apoptosis in human neuroblastoma cells. Finally, this study found that patients bearing MYCN-amplified tumors showed improved survival when SMC2 expression was low. These results identify novel functions of SMC2 in DNA damage response, and we propose that SMC2 (or the condensin complex) is a novel molecular target for the treatment of MYCN-amplified neuroblastoma.
Volume 13(7)
Pages 1115-31
Published 2014-1-1
DOI 10.4161/cc.27983
PII 27983
PMID 24553121
PMC PMC4013162
MeSH Adenosine Triphosphatases / metabolism Animals Apoptosis / genetics Carrier Proteins / genetics Carrier Proteins / metabolism* Cell Line, Tumor Chromosomal Proteins, Non-Histone / genetics Chromosomal Proteins, Non-Histone / metabolism DNA Damage / genetics Genome-Wide Association Study HEK293 Cells Humans Mice N-Myc Proto-Oncogene Protein Neuroblastoma / metabolism* Nuclear Proteins / genetics Nuclear Proteins / metabolism* Oncogene Proteins / genetics Oncogene Proteins / metabolism* Proto-Oncogene Proteins / genetics Proto-Oncogene Proteins / metabolism
IF 3.259
Times Cited 16
DNA material CSII-CMV-RfA-IRES2-Venus (RDB04388) CSII-CMV-Venus (RDB05553).