Actions and Substrates for the HER4 Tyrosine Kinase in Breast Cancer.
Annual rept. 1 Jul 97-30 Jun 98
NORTH CAROLINA UNIV AT CHAPEL HILL
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During the second year of our HER4 grant we have made progress in developing methods and cell lines to study the unique role of HER4 in stopping breast cancer growth. We have made a full length HER4 cDNA and have used site directed mutagenesis to create dominant negative mutations both in the HER4 tyrosine kinase domain and as a truncation mutant that will block HER4 activation. We have created inducible promoters that will express HER4 and dominant negative HER4 to more precisely control expression in breast cancer cell models. We have created two clonal lines expressing ECF receptor HER4 chimera in indicator cells. These express significantly different amounts of chimera. The biologic and tyrosine kinase activity and growth suppression differs markedly in these two lines. We have created constructs to make transgenic mice to prove that HER4 will block breast cancer development. Lastly, we have successfully raised one antisera and are making the HER4 extracellular domain in baculovirus for use as immunogen for monoclonal antibodies.
- Anatomy and Physiology
- Medicine and Medical Research