NASA Scientific and Technical Aerospace Reports
NASA Scientific and Technical Aerospace Reports
NASA Scientific and Technical Aerospace Reports
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several similar genetic epidemiological studies. The screening of sequence variants in ESR1, as well as the genotyping of both<br />
ESR1 <strong>and</strong> ESR2, are both ongoing. The analyses <strong>and</strong> results are expected during the rest of the training period.<br />
DTIC<br />
Cancer; Estrogens; Prostate Gl<strong>and</strong>; Risk<br />
20040111699 Georgetown Univ., Washington, DC<br />
The Regulation of the Angiogenic Factor FGF Binding Protein (FGF-BP) by the APC/Beta-Catenin Signaling Pathway<br />
in the Progression of Breast Cancer<br />
Stylianou, Dora C.; May 2004; 16 pp.; In English; Original contains color illustrations<br />
Contract(s)/Grant(s): DAMD17-01-1-0253<br />
Report No.(s): AD-A425854; No Copyright; Avail: CASI; A03, Hardcopy<br />
Fibroblast growth factor binding protein (FGF-BP) releases immobilized FGFs from the extracellular matrix <strong>and</strong> can<br />
function as an angiogenic switch molecule in cancer. We have determined that FGF-BP is upregulated in a portion of breast<br />
cancers <strong>and</strong> this upregulation is correlated with increased expression of beta-catenin. In this grant we hypothesized that<br />
beta-catenin can initiate angiogenesis in mammary carcinoma through FGF-BP. The aims were 1) to study the expression of<br />
FGF-BP in mammary tumorigenesis progression of the APC/+ mouse <strong>and</strong> 2) to determine the mechanism of regulation of<br />
FGF-BP b the APC/beta-catenin signaling pathway in breast cancer. To date, we have shown a positive correlation of<br />
upregulation of beta-catenin expression <strong>and</strong> FGF- BP in breast <strong>and</strong> other tumors in the APC/+ mice. We have also shown that<br />
beta-catenin can directly induce FGF-BP gene expression through a transcriptional mechanism <strong>and</strong> that a TCF site in the<br />
FGF-BP promoter is responsible for a major portion of this effect. To further study the nature <strong>and</strong> specificity of this interaction,<br />
we performed gel shift assays <strong>and</strong> determined that the TCF site at -1030 in the FGF-BP promoter is necessary for this<br />
interaction.<br />
DTIC<br />
Cancer; Fibroblasts; Mammary Gl<strong>and</strong>s; Proteins<br />
20040111700 Texas A&M Univ., College Station, TX<br />
FGF Signaling <strong>and</strong> Dietary Factors in the Prostate<br />
Wang, Fen; Mar. 2004; 25 pp.; In English<br />
Contract(s)/Grant(s): DAMD17-03-1-0014<br />
Report No.(s): AD-A425856; No Copyright; Avail: CASI; A03, Hardcopy<br />
Purpose: To study the FGF signaling axis in prostate homeostasis <strong>and</strong> tumorigenesis, to evaluate dietary factors in<br />
modulating FGF signals in the prostate. Scope: to develop mouse models resembling human prostate tumor progressions for<br />
screening therapeutic strategies for prostate cancers <strong>and</strong> evaluating dietary factors in prostate cancer prevention. Major<br />
Finding: Ectopic expression of the constitutively-active GFGR1 (caGFGR1) in the prostate induces high-grade prostatic<br />
intraepithelial neoplasia (PIN) in transgenic mice. The development of PIN <strong>and</strong> degree of homeostasis perturbation in the<br />
prostate are caFGFR1 expression level-dependent. Repression of the resident FGFR2 in the prostate poentiated the lesions<br />
induced by the ectopic caGFGR1. Up-to-date Progress: The major findings are published in Cancer Research. We have<br />
established mouse colonies with prostate-specific disruption of Fgfr2 loci <strong>and</strong> expression of the ectopic caFGFR1 for further<br />
characterizations of the FCF signaling <strong>and</strong> dietary factors in prostate lesions. Significance: Together with previous data form<br />
the Dunning prostate tumor model, the findings demonstrate that aberrant FGF signals in the prostate strongly disrupt tissue<br />
homeostasis, <strong>and</strong> promote prostate tumor development <strong>and</strong> progression. - The model provides a useful tool for evaluating other<br />
tumor initiating factors, including those that cause genetic instability <strong>and</strong> other oncoqenic lesions in prostrate tumorigenesis.<br />
DTIC<br />
Cancer; Diets; Nutrition; Prostate Gl<strong>and</strong><br />
20040111704 California Univ., Los Angeles, CA<br />
Microlocalization <strong>and</strong> Quantitation of Risk Associated Elements in Gleason Graded Prostate Tissue<br />
Eckhert, Curtis; Mar. 2004; 12 pp.; In English<br />
Contract(s)/Grant(s): DAMD17-03-1-0067<br />
Report No.(s): AD-A425860; No Copyright; Avail: CASI; A03, Hardcopy<br />
Epidemiological <strong>and</strong> laboratory studies show that boron, selenium <strong>and</strong> zinc reduce prostate cancer risk whereas calcium<br />
<strong>and</strong> cadmium increase risk. The objective of this proposal is to determine the concentration <strong>and</strong> location of these elements in<br />
normal <strong>and</strong> tumor tissue. Specific aims include: (1) preparation of four grades of prostate tissue, (2) determination of tissue<br />
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