Model showing erbB2 promoter status in human breast cancers with different levels of erbB2 expression (Mungamuri et al, Cell Reports 2013)

Elucidation of Breast Cancer Oncogenes

We have a long term research interest in breast cancer. Some of our earliest efforts to identify human oncogenes led to identification and cloning of erbB2 as a v-erbB related gene amplified in a primary human breast cancer and our demonstration of its transforming activity. These findings provided technology utilized to identify erbB2 amplified breast cancers and helped pave the way for biologically targeted therapies directed against the overexpressed tyrosine kinase receptor encoded by this gene. In recent studies, we have characterized chromatin modifications that sequentially enhance erbB2 expression levels in this breast tumor subtype with the goal of identifying new targets for therapeutic intervention in drug resistant tumors. We have also identified Wnt activation in a major subset of triple negative breast tumors (erbB2/HER2, ER, PR negative) and are presently characterizing target genes responsible for the Wnt invasive phenotype. Inflammatory breast cancer (IBC) is a particularly aggressive but rare form of breast cancer, which commonly metastasizes prior to detection. We established an IBC line, which reproduces the features of this aggressive tumor in immunocompromised mice and are presently investigating the molecular basis for the IBC phenotype.