Detecting and Targeting Oncogenic Myc in Breast Cancer
Final rept. 10 May 2004-9 May 2007
UNIVERSITY HEALTH NETWORK TORONTO (ONTARIO)
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Deregulation of the cellular myc proto-oncogene is one of the strongest activators of tumorigenesis and understanding the target genes regulated by this transcription factor in cancer etiology will clearly mark a key advance. Here we identify the non-coding RNA H19 as a Myc-induced gene that plays a functional role in breast cancer development. We have also developed antibody reagents to TRRAP, a cofactor that collaborates with Myc to drive tumorigenesis. To determine which target genes are co-regulated by Myc and TRRAP in breast cancer, we have optimized a ChIP-on-chip protocol Chromatin immunoprecipitation coupled with microarray technology that can be used with breast cancer cells and primary specimens to achieve both sensitive and specific results. We have also mapped two regions of TRRAP that interact with Myc as shown by co-immunoprecipitation. Our work will impact breast cancer research in several ways. The refined ChIP-on-chip protocol will be used by ourselves and others to conduct breast cancer research focused on specific transcription factors, such as Myc, as well as other regulatory mechanisms at the level of chromatin e.g. replication, DNA repair. In addition to several valuable antibody reagents, we have identified a novel Myc binding domain of TRRAP and we have identified H19 as a molecular target for the development of novel anti-cancer therapeutics.
- Genetic Engineering and Molecular Biology
- Medicine and Medical Research