Michael C. Burke
B.S. Rhodes College, 2005

1st Year Graduate Student

Advisor: Ken-Ichi Takemaru, Ph.D.

Department: Pharmacological Sciences

Graduate Program: Genetics

Abstract (rotation):

Advisor: Dr. W. Todd Miller, Department of Physiology & Biophysics, SBU

Title:  Brk silencing in mammary epithelium depotentiates metastatic signaling from ErbB2

Michael Burke, Kiranam Chatti, and W. Todd Miller

Ectopic expression of the non-receptor tyrosine kinase Protein Kinase 6 (Ptk6), colloquially known as Breast tumor kinase (Brk), has been identified in two-thirds of all breast cancers. In normal physiology, Brk potentiates signaling from the Epidermal Growth Factor family of receptors at terminally differentiated cells of the gastrointestinal tract; however, when expression is upregulated in a cancerous somatic cell-line it promotes cellular proliferation and metastases through SAM68, SLM, BKS, and Paxillin. Recent studies have revealed stable Brk binding, upon autophosphorylation of ErbB2 dimers, is associated with both increased phosphorylation and activation of Brk resulting in increased cellular proliferation. Using adenoviral transduction of plasmids containing bidirectional cassettes into the immortalized, mammary MCF-10A cell-line we employed a siRNA system to examine the knockdown of Brk on ErbB2 induced cellular proliferation through immunochemistry and bromodeoxyuridine incorporation.