Assessment of the Activation State of RAS and Map Kinase in Human Breast Cancer Specimens (96Breast)
Abstract
We found that Ras was highly activated in 11 of 20 breast cancers compared to normal tissue; 7 of these 11 cancers expressed both the epidermal growth factor (EGF) and ErbB-2/neu/HER-2 receptors with the remaining four cancers with high Ras activation expressing one of these two receptors. In the other 9 cancers, Ras activation was similar to that observed in normal breast tissue with none of these cancers expressing the E&F receptor while one expressed the ErbB-2 receptor. None of the cancers tested had an activating K-ras mutation nor did any of the cancers express a truncated E(iF receptor or the c-FMS receptor. The activity of mitogen- activated protein (MAP) kinase was high in the cancers and reflected the degree of Ras activation. In cultured mammary tumor cell lines, we showed that Ras activation was ligand dependent in cells overexpressing the ErbB-2 receptor. Thus, Ras was abnormally activated in breast cancers overexpressing the EGF and/or ErbB-2 receptors indicating there are sufficient ligands in vivo to activate these receptors and this work provides a basis for new target-based treatments of this disease. Using a newly-developed assay, we are now in the process of measuring the activation state of Rho, a Ras-related protein that has been shown to play a role in carcinogenesis.
Document Details
- Document Type
- Technical Report
- Publication Date
- Sep 01, 1999
- Accession Number
- ADA380388
Entities
People
- Gerry Boss
Organizations
- University of California, San Diego