Rapid Visual Assays of Oncogenic Aberrant ErbB Receptor Activation Using Fluorescence Microscopy

摘要

The growth of cells in the body is closely regulated by peptide growth factors, which are detected by the cells via cell-surface receptors. Many human cancers of the breast, brain, etc., can develop if these receptors behave as if they sense the presence of growth factors when they should not. One particular family of receptors that has been heavily implicated in the development of human cancers is the ErbB receptor tyrosine kinase family, which includes both the EGF-Receptor and ErbB2/HER-2/neu - both of which are major targets for chemotherapeutic agents either in clinical use or in clinical trials. The physiologic outcome of both normal and oncogenic ErbB receptor activation depends on the ability of these receptors to form both homo- and heteromeric complexes, but the exact mechanism underlying the formation of these complexes is not well understood. We have used a variety of cell biological, biochemical and biophysical approaches to elucidate the nature of homo- versus heteromeric complexes in the ErbB receptor family.