Journal
EXPERIMENTAL CELL RESEARCH
Volume 332, Issue 2, Pages 223-235Publisher
ELSEVIER INC
DOI: 10.1016/j.yexcr.2015.02.005
Keywords
Breast cancer; Gene amplification; Driver oncogene; TCP-1; CCT2
Categories
Funding
- Functional Genomics and Bioinformatics Facility in the Department of Pediatrics, Wayne State University School of Medicine
- Wayne State University School of Medicine C.S. Mott Applied Genomics Technology Center
- American Cancer Society Research Grant [IRG-97-219-14]
- Herrick Foundation
Ask authors/readers for more resources
Gene amplification is a common mechanism of oncogene activation in cancer. Several large-scale efforts aimed at identifying the comprehensive set of genomic regions that are recurrently amplified in cancer have been completed. In breast cancer, these studies have identified recurrently amplified regions containing known drivers such as HER2 and CCND1 as well as regions where the driver oncogene is unknown. In this study, we integrated RNAi-based functional genetic data with copy number and expression data to identify genes that are recurrently amplified, overexpressed and also necessary for the growth/survival of breast cancer cells. Further analysis using clinical data from The Cancer Genome Atlas specifically identified candidate genes that play a role in determining patient outcomes. Using this approach, we identified two genes, TCP1 and CCT2, as being recurrently altered in breast cancer, necessary for growth/survival of breast cancer cells in vitro, and determinants of overall survival in breast cancer patients. We also show that expression of TCPI is regulated by driver oncogene activation of PI3K signaling in breast cancer. Interestingly, the TCP1 and CCT2 genes both encode for components of a multi-protein chaperone complex in the cell known as the TCP1 Containing Ring Complex (TRiC). Our results demonstrate a role for the TRiC subunits TCPI and CCT2, and potentially the entire TRiC complex, in breast cancer and provide rationale for TRiC as a novel therapeutic target in breast cancer. (C) 2015 Elsevier Inc. All rights reserved.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available