FGF Signaling and Dietary Factors in the Prostate
Final rept. 1 Mar 2003-31 Aug 2006
TEXAS A AND M UNIV COLLEGE STATION HEALTH SCIENCE CENTER
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Purpose To study the FGF signaling axis in prostate homeostasis and tumorigenesis, to evaluate dietary factors in modulating FGF signals in the prostate. Scope To develop mouse models resembling human prostate tumor progressions for screening therapeutic strategies for prostate cancers and evaluating dietary factors in prostate cancer prevention. Major Finding Ectopic expression of the constitutively-active FGFR1 caFGFR1 in the prostate induces high-grade prostatic intraepithelial neoplasia PIN in transgenic mice in an expression level-dependent manner. Repression of the resident FGFR2 in the prostate also disturbs homeostasis in the prostate as well as potentiates the PIN lesions induced by the ectopic caFGFR1. Up-to-date Progress Establishing mouse colonies with prostate-specific FGFR2 disruption and caFGFR1 expression for further characterizations of the FGF signaling and dietary factors in prostate lesions. Generation of a conditional expression vector for expressing FGFR1 in the prostate. Characterization of the prostate of FGFR2 conditional null mice. Generation of 4 transgenic lines for conditional expression of caFGFR1 in the prostate. Significance Together with previous data from the Dunning prostate tumor model, the findings demonstrate that aberrant FGF signals in the prostate strongly disrupt tissue homeostasis and promote prostate tumor development and progression. The model provides a useful tool for evaluating other tumor initiating factors, including those that cause genetic instability and other oncogenic lesions in prostate tumorigenesis.
- Genetic Engineering and Molecular Biology
- Anatomy and Physiology
- Medicine and Medical Research