Fibroblast 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.
Additional contributors: Johanna Reed; TJ Beadnell; Lindsey Bade; Laura Bohrer; Jodi Goldberg; Kaylee Schwertfeger (faculty mentor)
Genetic Approach to Generating a Novel Mouse Model of Mammary Tumorigenesis.
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