Assessment of the Activation State of Ras and Map Kinase in Human Breast Cancer Specimens
Abstract
Although genetic ras mutations are infrequent in breast cancer, Ras may be pathologically activated in breast cancer by overexpression of growth factor receptors which signal through Ras. We measured Ras activation in 20 human breast cancers and seven non-malignant breast samples and found Ras was highly activated in 11 of the cancers, i.e., more than two standard deviations above the mean of the benign samples; seven of these 11 cancers expressed both the epidermal growth factor (EGF) and the ErbB-2/neu/HER-2 receptors with the remaining four cancers with high Ras activation expressing one of these two receptors. In the remaining 9 cancers, Ras activation was similar to that observed in the benign breast samples with none of these cancers expressing the EGF receptor while one expressed the ErbB-2 receptor. None of the cancers tested had an activating K-ras mutation. 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, kas is 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 human breast cancer.
Document Details
- Document Type
- Technical Report
- Publication Date
- Jan 01, 2001
- Accession Number
- ADA388934
Entities
People
- Gerry R. Boss
Organizations
- University of California, San Diego