Unknown

Dataset Information

0

Inactivation of SMC2 shows a synergistic lethal response in MYCN-amplified neuroblastoma cells.


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.

SUBMITTER: Murakami-Tonami Y 

PROVIDER: S-EPMC4013162 | BioStudies | 2014-01-01

REPOSITORIES: biostudies

Similar Datasets

2020-01-01 | S-EPMC7016506 | BioStudies
1000-01-01 | S-EPMC4785793 | BioStudies
2020-01-01 | S-EPMC7598076 | BioStudies
2020-01-01 | S-EPMC7076674 | BioStudies
2012-01-01 | S-EPMC3527934 | BioStudies
2015-01-01 | S-EPMC6207083 | BioStudies
1000-01-01 | S-EPMC6117286 | BioStudies
1000-01-01 | S-EPMC2695754 | BioStudies
2015-01-01 | S-EPMC4345284 | BioStudies
2017-01-01 | S-EPMC5763115 | BioStudies