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Ras activation in human breast cancer
F C von Lintig1, A D Dreilinger, N M Varki
1Department of Medicine, and Cancer Center, University of California, San Diego, La Jolla, USA.
Breast Cancer Research and Treatment
|September 16, 2000
Summary
Ras protein in breast cancer is often activated by growth factor receptor overexpression, not direct mutation. This study found high Ras activation in 11 of 20 breast cancers, linked to EGF and ErbB-2 receptors, suggesting new therapeutic targets.
Area of Science:
- Oncology
- Molecular Biology
- Biochemistry
Background:
- Genetic ras mutations are rare in breast cancer.
- Ras signaling can be abnormally activated by growth factor receptor overexpression.
- Epidermal Growth Factor (EGF) and ErbB-2/HER-2 receptors signal through Ras.
Purpose of the Study:
- To measure Ras activation in breast cancer tissues.
- To correlate Ras activation with growth factor receptor expression.
- To investigate potential therapeutic targets in breast cancer.
Main Methods:
- A highly sensitive, coupled enzymatic assay was used to measure Ras activation.
- Ras activation was analyzed in 20 breast cancers, 2 fibroadenomas, and 7 normal breast samples.
- Expression of EGF and ErbB-2/HER-2 receptors was assessed.
Main Results:
- Ras was highly activated in 11 of 20 breast cancers compared to benign tissue.
- High Ras activation correlated with overexpression of EGF and/or ErbB-2 receptors.
- Mitogen-activated protein (MAP) kinase activity reflected Ras activation levels.
- No activating K-ras mutations were found in the tested cancers.
Conclusions:
- Abnormal Ras activation occurs in breast cancers overexpressing EGF and/or ErbB-2 receptors.
- In vivo ligands are sufficient to activate these overexpressed receptors.
- This provides a basis for developing new target-based treatments for breast cancer.