Format

Send to

Choose Destination
Cell Cycle. 2014;13(7):1115-31. doi: 10.4161/cc.27983. Epub 2014 Feb 7.

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

Author information

1
Department of Molecular Biology; Nagoya University Graduate School of Medicine; Nagoya, Japan.
2
Department of Computer Science/Scientific and Engineering Simulation; Nagoya Institute of Technology; Nagoya, Japan.
3
Laboratory of Genome Structure & Function; Institute of Molecular and Cellular Biosciences; The University of Tokyo; Tokyo, Japan.
4
Department of Pediatrics and Center for Childhood Cancer Research; Children's Hospital of Philadelphia; University of Pennsylvania; Philadelphia, PA USA.
5
Division of Genetics; National Cancer Institute; Tokyo, Japan.
6
Division of Molecular Oncology; Aichi Cancer Center Research Institute; Nagoya, Japan; Division of Epigenomics; Aichi Cancer Center Research Institute; Nagoya, Japan.
7
Division of Molecular Oncology; Aichi Cancer Center Research Institute; Nagoya, Japan.
8
Department of Biological Science; Faculty of Science and Engineering; Chuo University; Tokyo, Japan.

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.

KEYWORDS:

DNA damage response; MYCN; condensin complex; neuroblastoma; synergistic lethal response

PMID:
24553121
PMCID:
PMC4013162
DOI:
10.4161/cc.27983
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for Taylor & Francis Icon for PubMed Central
Loading ...
Support Center