Mechanism of ErbB1 and ErbB2 Hetero-Oligomerization
Annual summary rept. 1 Jul 2001-30 Jun 2002
PENNSYLVANIA UNIV PHILADELPHIA
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We are developing an in vivo system using erbBIL2 receptor chimerae in a B-cell line to investigate the interactions and mechanism of oligomerization between the epidermal growth factor EGF receptor family members erbBl and erbB2. Since erbB2 overexpression has been strongly associated with breast cancer and has been shown to be a valuable target for breast cancer therapies, we are interested in dissecting its mechanism of activation. Heteromeric interaction between the intracellular domains of the IL2 receptor beta and gamma chain will serve as a reporter for direct interaction between the extracellular domains of erbBl and erbB2 by mediating T or B-cell proliferation in the absence of IL2. To date, I have made B-cell lines stably expressing various erbBIL2 receptor chimerae and I have been able to show erbBl homo-oligomerization and hetero-oligomerization with erbB2 in an EGF and IL2 independent manner. With this assay, I plan to assess the ability of specific erbB receptor ligands to induce erbBl and erbB2 hetero-oligomers and determine whether erbBl and erbB2 interact as a hetero-tetramer rather than a hetero-dimer. By understanding how erbBl and erbB2 interact, we hope to provide insight into the mechanism by which erbB2 mediates transformation and tumorigenicity in cells.
- Anatomy and Physiology
- Medicine and Medical Research