Effects of CSK Homologous Kinase Overexpression on HER2/Neu-Mediated Signal Transduction Pathways in Breast Cancer Cells
Annual summary rept. 1 Apr 2002-31 Mar 2003
BETH ISRAEL DEACONESS MEDICAL CENTER BOSTON MA
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Our proposal aims to investigate in details the potential function of CHK in breast cancer as a signal transducer in the signaling pathway from HER2Neu receptor. The studies conducted in the period reported included 1 the assessment of the effects of CHK on the main signaling pathways RAFTK-and Akt-mediated induced by the activation of HER2Neu receptor, 2 comparison of the effects in vitro of wild-type CHK and mutant forms enhancedabolished binding to HER2Neu receptor of this CHK on the heregulin-induced activation of Src-family kinases. Our major findings are as follows la CHK directly associates with RAFTK kinase and is a negative regulator of RAFTK activation in HER2Neu elicited transduction pathway lb CHK under some circumstances facilitates activation of Akt following activation of HER2Neu receptor 2 the effects of CHK on Src kinase activation are directly coupled with the ability of CHK to bind the activated form of HER2Neu receptor.
- Medicine and Medical Research