Characterization of IKBKE as a Breast Cancer Oncogene
Abstract
Previous work in the Hahn Lab has identified IKBKE as a novel breast cancer oncogene that is capable of human mammary cell transformation. Amplification and overexpression of IKKepsilon was observed in a significant percentage of human breast cancer cell lines and primary tumor samples. Additionally, breast cancer cell lines carrying the IKBKE amplicon showed decreased viability in response to IKKepsilon suppression by shRNA. Our work has also demonstrated that IKKepsilon is a non-canonical IKK (IkappaB kinase) family member that activates the NF-kappaB pathway and that this activity is essential for cell transformation. However, it is known that IKKepsilon not does participate in the canonical IKK complex to activate NF-kappaB signaling. Though recent work has sought to identify the downstream targets of IKKepsilon, the mechanism of its upstream regulation is not well-understood. Thus, I propose to further our understanding of IKKepsilon function by investigating the upstream regulation of IKKepsilon - specifically, the role of ubiquitination in IKKepsilon-mediated cell transformation. In addition, I am to investigate the role of IKKepsilon in breast cancer initiation and maintenance in vivo through the generation of a constitutive and an inducible transgenic mouse model.
Document Details
- Document Type
- Technical Report
- Publication Date
- Oct 01, 2009
- Accession Number
- ADA515797
Entities
People
- Alicia Zhou
Organizations
- Dana–Farber Cancer Institute