Format

Send to

Choose Destination
Oncogene. 2003 Aug 14;22(34):5358-61.

Amplification and overexpression of COPS3 in osteosarcomas potentially target TP53 for proteasome-mediated degradation.

Author information

1
Department of Tumour Biology, Institute of Cancer Research, The Norwegian Radium Hospital, 0310 Oslo, Norway.

Abstract

In sarcomas, the TP53 tumour suppressor pathway may be altered either by TP53 mutations or by amplification of MDM2, encoding a protein that inhibits TP53 and targets it for 26S-proteasome degradation. However, in the majority of the analysed clinical samples, neither of these types of aberrations are found, suggesting that additional mechanisms are involved. The present study shows that COPS3, located in 17p11 and encoding a component of the proteasome pathway, is more frequently amplified in osteosarcomas (OS) than is MDM2. We present detailed analysis of TP53 mutations and MDM2 and COPS3 expression levels in a set of 23 OS. Our results show that none of the tumours with COPS3 amplification had MDM2 amplification nor TP53 mutations, consistent with the hypothesis that one of the three aberrations is sufficient. The results suggest that inactivation of otherwise intact TP53 by aberrations in the proteasome pathway may contribute to the characteristic aneuploidy observed in OS.

PMID:
12917637
DOI:
10.1038/sj.onc.1206671
[Indexed for MEDLINE]

Supplemental Content

Full text links

Icon for Nature Publishing Group Icon for Norwegian BIBSYS system
Loading ...
Support Center