Genetic Approach to Generating a Novel Mouse Model of Mammary Tumorigenesis
2011-04-13
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Genetic Approach to Generating a Novel Mouse Model of Mammary Tumorigenesis
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2011-04-13
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Abstract
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.
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Additional contributors: Johanna Reed; TJ Beadnell; Lindsey Bade; Laura Bohrer; Jodi Goldberg; Kaylee Schwertfeger (faculty mentor)
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Miller, Matthew. (2011). Genetic Approach to Generating a Novel Mouse Model of Mammary Tumorigenesis. Retrieved from the University Digital Conservancy, https://hdl.handle.net/11299/105038.
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