Role of PTPase LAR in EGF Receptor in the Mammary Gland
Abstract
The epidermal growth factor receptor(EGFR) is an important mediator of breast cancer tumorigenesis and metastasis. While much is known about EGFR signal transduction related to its tyrosine kinase activity, less is known about the protein tyrosine phosphatases (PTPs) which must be present to modulate the cellular effects of the EGFR by dephosphorylating the receptor and its substrates. Evidence derived from several approaches suggests that the transmembrane PTP LAR may be involved in EGFR signaling in mammary gland development and tumorigenesis. The hypothesis to he tested in this proposal is that LAR plays an important role in EGFR-dep en dent mammary gland development and tumorigenesis through negative modulation of EGFR signal transduction. Work in the first year has% supported this hypothesis. EGF receptor signaling was shown to be increased in SV40-immortalized cells from LAR - knockout mice. Cell density influenced the magnitude of the effect. LAR expression is also shown to be regulated by cell density, with concentrations increasing markedly as cell density increases. Functional E-cadherin complexes are necessary for this effect. It is intriguing to speculate that the density dependent increase in LAR is involved in the suppression of EGF signaling. Finally, we have now developed a transgenic mouse with targeted expression of human LAR to the mammary gland. Characterization of mammary gland development and tendency to tumorigenesis will be pursued. This will be an important complement to our parellel studies of development and tumorigenesis in the LAR knockout mouse.
Document Details
- Document Type
- Technical Report
- Publication Date
- Jun 01, 2001
- Accession Number
- ADA396369
Entities
People
- Robert A. Mooney
Organizations
- University of Rochester