Compartmentalized Signaling and Breast Cancer Cell Proliferation
Abstract
This proposal will test a unique hypothesis that Src-family kinases direct the ErbB receptor traffic into an intracellular compartment where proliferation signals are generated. This hypothesis is based on observations that while Cbl proto-oncoprotein facilitates the down-regulation of ErbB receptors from cell surface and functions as a negative regulator, Src tyrosine kinase enhances paradoxically enhance both the internalization of EGFR and the EGFR-mediated mitogenic signals. The proposed studies will test this hypothesis using mammary epithelial cells made to overexpress EGFR or ErbB together with Src. The insights gained from this model system will be directly relevant to a large proportion of breast cancers where ErbB receptors and Src-family kinases are co-overexpressed. Validation of our hypothesis will represent a shift in the current paradigm of normal and aberrant ErbB receptor signaling and may provide novel targets for therapeutic intervention relevant to ErbB-overexpressing breast cancers, which carry a significantly worse prognosis and are frequently hormone-unresponsive.
Document Details
- Document Type
- Technical Report
- Publication Date
- Jul 01, 2001
- Accession Number
- ADA400191
Entities
People
- Hamid Band
Organizations
- Brigham and Women's Hospital