Characterization of the Role of Breast Tumor Kinase (BRK) in Breast Cancer Cells Non-responsive to EGFR-targeted Agents
Annual rept. 22 Jun 2005-21 Jun 2006
STATE UNIV OF NEW YORK AT STONY BROOK
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Epidermal growth factor EGF receptor tyrosine kinases erbB family EGFR erbB1 and HER2 are highly expressed in breast cancer and are associated with poor prognosis. A number of EGFR andor HER2-targeted agents are being investigated for breast cancer treatment. Brk Breast Tumor Kinase is a nonreceptor tyrosine kinase that has been shown to enhance the mitogenic signaling of EGF induce phosphorylation of erbB 3 and interact with AKT. In this study we aim to investigate whether Brk can promote cells to become refractory to EGFR-targeted drugs. PI-3 kinaseAKT pathway mediates EGF-induced cell growth and survival and is involved in cellular resistance to anti-cancer drugsAKT pathway is regulated by multiple activators downregulation of the EGFR alone may not lead to its inhibition. We will investigate whether Brk promotes growth and survival as well as PI3KIAKT activity in cells treated with EGFR-targeted agents.
- Medicine and Medical Research