Role of the erbB3 Gene Product in Breast Cancer Cell Proliferation
Annual rept. 1 Sep 95-31 Aug 96
IOWA UNIV IOWA CITY
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The role of the ErbB3 protein in breast cancer cell proliferation was examined. In previous studies, we investigated the signal transduction mechanism of the ErbB3 protein, which cooperates with ErbB2 in the formation of a coreceptor for the growth factor heregulin. We demonstrated that the ErbB3 protein, although possessing a protein tyrosine kinase PTK homology domain, is in fact devoid of intrinsic PTK activity. In the second year of funding, we have demonstrated the critical dependence of heregulin signalling upon the PTK activity of ErbB2. To this end, the PTK domain of ErbB2 was mutated, such that its intrinsic kinase activity was abolished, and this mutant ErbB2 protein was expressed along with wild-type ErbB3 in cultured cells. Our results indicated that the ErbB2 mutation abolished heregulin signal transduction. We also characterized the interaction of ErbB3 with the p85 subunit of phosphatidylinositol 3-kinase, an enzyme known to be involved in heregulin signalling. By use of the yeast two-hybrid system, we mapped the sites of interaction between ErbB3 and p85. Finally, we have pursued the cloning of the heregulin gene promoter, in effort to understand the regulation of heregulin expression in breast cancer cells.
- Genetic Engineering and Molecular Biology
- Anatomy and Physiology
- Medicine and Medical Research