Browsing by Author "Miller, Matthew"
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Item Genetic Approach to Generating a Novel Mouse Model of Mammary Tumorigenesis(2011-04-13) Miller, MatthewFibroblast growth factor receptors (FGFRs) and their ligands contribute to cellular functions including proliferation, survival, differentiation, migration, and angiogenesis. The growth factor receptor, FGFR1, chromosomal locus is amplified in 10% of breast cancer patients. Patients with this amplification do not respond well to current therapies and have been shown to develop a resistance to endocrine therapies, thus the inducible fibroblast growth factor receptor-1 (iFGFR1) was engineered. When activated, iFGFR1 promotes increased lateral budding of epithelial structures which develop into hyperplasias that progress to multicellular invasive lesions, characteristic of breast cancer. One pro-inflammatory protein upregulated by iFGFR1 activation is osteopontin. Osteopontin is a secreted glycophosphoprotein that is involved in a variety of different cancer types, including breast cancer. Data suggests that osteopontin is synthesized by breast carcinomas and acts to promote traits associated with increased aggressiveness. To study iFGFR1-induced osteopontin expression and the role osteopontin plays in cancer development and progression in mouse mammary glands in vivo, I developed a novel mouse model where mice are heterozygous for our FGFR transgene and osteopontin null (FGFR1 +/-; osteopontin -/-). In order to do this I backcrossed osteopontin -/- mice on a C57BL/6 genetic background to the FVB genetic background of the FGFR1 mice. The goal of this project was to master techniques in mouse husbandry and PCR-based genotyping as well as tissue staining. With the new transgenic mouse model we can better study the correlation between osteopontin levels and breast cancer in hopes of making osteopontin a targetable factor for therapeutic intervention.