Characterization of the Heregulin-Stimulated Activation of the Neu/ErB2 Tyrosine Kinase and Its Involvement in Breast Cancer.
Annual rept. 15 Jul 95-14 Jul 96,
CORNELL UNIV ITHACA NY
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In this report, we describe our progress during the past year June 15, 1995 to June 15, 1996 in studying different aspects of the signaling pathways initiated by the EGF receptor and the related Neu and ErbB2 tyrosine kinase. We have obtained evidence for a novel mechanism for growth factor signaling where growth factor-stimulated dimerization events e.g. between the EGF receptor and Neu or between Neu and ErbB3 are transient and give rise to secondary receptor dimers. We also have obtained increasing evidence for the importance of two new signaling molecules, the c-Cbl protein and an 18 kDa nuclear GTP-binding protein p18 in the actions of the EGF receptor and Neu. In the coming year, we intend to extend these studies and identify the specific cellular proteins that are activated in human breast cancer cells following primary and secondary receptor dimerization events. We also will determine whether the Cbl proto-oncogene product serves to interface the EGF receptor with the Cdc42 GTP-binding protein in breast cancer cells and gives rise to a signaling pathway that culminates in the activation of p18. Finally, we will determine if identical signaling pathways are operating in dog mammary carcinomas as an important step toward validating this system as a model for human breast cancer.
- Anatomy and Physiology