A Novel Mouse Model for Genetic Validation of Therapeutic Targets in Breast Cancer
Abstract
Identifying the optimal molecular targets for effective and specific treatment of breast carcinoma is limited by our ignorance of which molecular pathways or network nodes are critical for the initiation, evolution and, above all, maintenance of breast cancers. Our overarching hypothesis is that although tumors appear genetically complex, they most probably are dependent upon a very much more limited repertoire of mutations for their maintenance. To test this hypothesis, we proposed to construct a novel type of mouse cancer model in which endogenous genes encoding critical signaling molecules are modified so that there expression can be toggled on and off at will by the action of ligand-dependent heterologous repressors. Using such heterologous repressor targeting (HRT), we will directly ascertain the requirement for such signaling molecules in normal breast epithelial development and maintenance and for mutant forms of such molecules in driving and maintaining breast cancers. Our initial focus within the BCRP proposal is on c-myc and e2f3 genes, both of which encode pleiotropic transcription factors whose deregulated activities are causally implicated in breast (and other) cancers.
Document Details
- Document Type
- Technical Report
- Publication Date
- Jun 01, 2006
- Accession Number
- ADA462839
Entities
People
- Gerardi Evans
Organizations
- University of California, San Francisco