Protein Kinases in Human Breast Carcinoma
Abstract
This project focuses on the biology of the Rak protein tyrosine kinase in human breast cancer. Rak is a novel tyrosine kinase our group has identified in breast cancer tissues and cell lines that has structural homology to the Src tyrosine kinase, with SH2 and SH3 domains at its amino terminus. Rak appears to be a potent growth inhibitory gene in breast cancer as induction of its expression causes cells to detach from their substratum, float in the medium, and undergo apoptosis as determined by TUNEL assay. BrdU incorporation in Rak expressing cells confirms these results. FACS analysis shows that Rak expression induces a G1 arrest that is Rb and p53 independent. Rak expression also protects cells from the effects of Taxol. Western analysis shows that Rak is expressed in a subset of human tumors, and often appears upregulated in the nodal metastases. We are also pursuing a possible interaction of Rak with the Rho family of GTPases. Through cell culture, molecular biology, and human tissue analysis we hope to further characterize the biology of this unique protein and determine is suitability as a therapeutic target.
Document Details
- Document Type
- Technical Report
- Publication Date
- Jul 01, 1999
- Accession Number
- ADB253637
Entities
People
- William G. Cance
Organizations
- University of North Carolina at Chapel Hill