Journal
ONCOGENE
Volume 33, Issue 3, Pages 308-315Publisher
NATURE PUBLISHING GROUP
DOI: 10.1038/onc.2012.596
Keywords
glioma; p21; PDGF; stem/progenitor; TRIM3
Funding
- Memorial Sloan-Kettering Cancer Center Core Grant [P30CA08748]
- Brain Tumor Center
- Golfers Against Cancer Foundation
- [CA89563]
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The TRIM family of genes is largely studied because of their roles in development, differentiation and host cell antiviral defenses; however, roles in cancer biology are emerging. Loss of heterozygosity of the TRIM3 locus in similar to 20% of human glioblastomas raised the possibility that this NHL-domain containing member of the TRIM gene family might be a mammalian tumor suppressor. Consistent with this, reducing TRIM3 expression increased the incidence of and accelerated the development of platelet-derived growth factor -induced glioma in mice. Furthermore, TRIM3 can bind to the cdk inhibitor p21(WAF1/CIP1). Thus, we conclude that TRIM3 is a tumor suppressor mapping to chromosome 11p15.5 and that it might block tumor growth by sequestering p21 and preventing it from facilitating the accumulation of cyclin D1-cdk4.
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