Role of PTPase LAR in EGF Receptor in the Mammary Gland
Abstract
The epidermal growth factor receptor (EGFR) and the related protein erbB2 have been implicated as important mediators 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) that 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. Two sets of data are particularly important. First, the LAR knockout mouse has been shown to have a defect in terminal mammary gland development. Second, we have shown that suppression of cellular LAR by 60% using an antisense expression vector results in a 3-4 fold elevation of EGF- dependent receptor signaling. Based upon these and other observations, the hypothesis to be tested in this proposal is that LAR plays an important role in EGFR-dependent mammary gland development and tumorigenesis through negative modulation of EGFR signal transduction.
Document Details
- Document Type
- Technical Report
- Publication Date
- Jun 01, 2003
- Accession Number
- ADA421766
Entities
People
- Robert A. Mooney
Organizations
- University of Rochester