NASA Scientific and Technical Aerospace Reports

form of ErbB-2. One of these cleavage events occurs in the carboxyterminal domain of ErbB-2, while another takes place in
the kinase domain. We have identified sequences within the kinase domain that are required for this molecule’s sensitivity to
geldanamycin. Once these initial cleavage events occur the resultant fragments of ErbB-2 are rapidly degraded. However,
these fragments may induce novel biologic activities within cells particularly if ErbB-2 is overexpressed. We have identified
a short sequence within the kinase domain of ErbB-2 that is able to induce cell death. This could account for the cellular
toxicity of geldanamycin.
DTIC
Cancer; Mammary Glands; Metabolism; Stability
20040111757 Texas Univ., Dallas, TX
Development of a Novel In-Situ Telomere Length Qualification System to Address Suitability of Telomerase Inhibitor
Therapy to Breast Cancer
Forsyth, Nicholas R.; Apr. 2004; 19 pp.; In English
Contract(s)/Grant(s): DAMD17-01-1-0420
Report No.(s): AD-A425971; No Copyright; Avail: CASI; A03, Hardcopy
The ability to predetermine therapeutic intervention times following tumor resection would be invaluable to patient well
being and clinical resources. We sought to determine if we could establish a methodology where in vivo tumor telomere length
could be established using in situ hybridisation as a quantitative tool. This technique would require development, validation,
and application to a model system. A three dimensional technique to measure telomere length was established. This technique
was applied to breast cancer derived tumor cell lines thereby establishing technique, methodology, and validity. In vivo
application was established using both a readily available tissue source and tumors derived from tumorigenic breast cancer
cell lines. Combining the approach to breast cancer cell lines we were then able to approximate at required times of telomerase
inhibition before driving the cells into telomere-driven replicative senescence. This technique represents an important
development in the ability to measure telomere length in vivo and ultimately could become appropriate for clinical application.
DTIC
Cancer; Cells (Biology); Inhibitors; Mammary Glands; Qualifications; Therapy
20040111758 Southern Research Inst., Birmingham, AL
Inactivation of FGF Receptors by Targeting Ribozymes Against FGFR mRNAs and Their Effect on FGF Dependent
In Vitro and In Vivo Breast Cancer Growth Phenotypes
Estes, Norman R.; May 2004; 16 pp.; In English
Contract(s)/Grant(s): DAMD17-01-1-0400
Report No.(s): AD-A425972; No Copyright; Avail: CASI; A03, Hardcopy
Acquired tamoxifen resistance is common in breast cancer patients with estrogen receptor positive (ER+) tumors. Growth
factor signaling can provide ER+ breast cancer cells with alternative growth stimulus to that provided by activation of ER.
In order to determine whether an individual FGF receptor (FGFR) or multiple receptors are responsible for conferring an
alternate growth signaling pathway, we are using a siRNA targeting strategy to selectively inactivate each of the receptors
either singly or in combination. We have screened siRNA designed in our lab or commercially available siRNA targeting each
FGFR and shown their ability to reduce target mRNA levels using transient transfection assays. These assays have indicated
that siRNAs designed against each receptor are able to at least partially reduce target mRNA as determined by quantitative
RT-PCR. Using these sequences, we have developed clonal and polyclonal cell lines that stably express shRNA against all 4
FGFRs. We have also developed shRNA expressing vectors that also express EGFP and are currently using these vectors to
determine cell cycle progression in ML-20 cells expressing the shRNA under FGF dependent conditions.
DTIC
Cancer; Deactivation; Estrogens; Fibroblasts; In Vitro Methods and Tests; In Vivo Methods and Tests; Mammary Glands;
Receptors (Physiology); Ribonucleic Acids
20040111759 Meharry Medical Coll., Nashville, TN
Is Peripheral Benzodiazepine Receptor (PBR) Gene Expression Involved in Breast Cancer Suppression by Dietary
Soybean Protein
Das, Salil K.; Jun. 2004; 14 pp.; In English
Contract(s)/Grant(s): DAMD17-03-1-0352
Report No.(s): AD-A425974; No Copyright; Avail: CASI; A03, Hardcopy
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