Effects of Csk Homologous Kinase Overexpression on HER2/Neu-Mediated Signal Transduction Pathways in Breast Cancer Cells
Abstract
Our proposal aimed to investigate the potential function of CHK as a signal transducer in the signaling pathway from HER2/Neu receptor. Our major accomplishments are as follows: 1) a) We described the effects of CHK on the HER2/Neu signal transduction towards RAFTX and kt kinases. b) We have identified modulation by CHX of CXCR4 expression in breast cancer cells. 2) a) We described the correlation of the binding affinity of CHK to HER2/Neu with the effectiveness of the inhibition Cf Src kinase by CHIC. b) We evaluated the role of CHIC in the development of Neu induced mammary tumors in transgenic mice. 3) We generated CHIC protein derivatives and evaluated their usefulness as potential tools for protein therapy of breast cancer in vitro. Our results confirm the notion that CHIC is a signal transduction modulator HER2/Neu-mediated pathway in breast cancer cells. However, the effects elicited by CHIC are ambiguous. CHIC is capable of elic iting both inhibitory and stimulatory effects in breast cancer cells. The results obtained in transgenic mouse model do not reaffirm the potential role of CHK in formation of Neu-induced mammary carcinomas. However, in the inhibitory effects of CHIC suggest potential role of CHIC in breast cancer invasion and metastasis. These findings warrant further investigations.
Document Details
- Document Type
- Technical Report
- Publication Date
- Apr 01, 2005
- Accession Number
- ADA436916
Entities
People
- Hava Avraham
- Radoslaw Zagozdzon
Organizations
- Beth Israel Deaconess Medical Center