NASA Scientific and Technical Aerospace Reports
NASA Scientific and Technical Aerospace Reports
NASA Scientific and Technical Aerospace Reports
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20040111555 Baylor Coll. of Medicine, Houston, TX<br />
A Unique Breast Cancer Cell Model for Studying Reported Functions of Membrane-Localized Estrogen Receptor<br />
Lee, Adrian V.; Apr. 2004; 9 pp.; In English; Original contains color illustrations<br />
Contract(s)/Grant(s): DAMD17-02-1-0286<br />
Report No.(s): AD-A425595; No Copyright; Avail: CASI; A02, Hardcopy<br />
We previously developed a cell line system in which exogenous expression of estrogen receptor alpha (ERalpha) in an<br />
ERalpha-negative cell line resulted in ERalpha -mediated signaling <strong>and</strong> proliferation. We have now generated cell lines that<br />
express ERalpha only in the cytoplasm (cERalpha) to characterize the putative cytoplasmic (non- genomic) function of<br />
ERalpha. We have found that the cERalpha can bind estrogen <strong>and</strong> is down-regulated, similar to wild-type ERalpha.<br />
Intriguingly, the cERalpha is completely resistant to 1C118278O-mediated degradation. cERalpha can’t activate gene<br />
transcription (due to its inability to enter the nucleus), <strong>and</strong> also can’t stimulate cell cycle progression. Consistent with the<br />
cERalpha not activating gene transcription or cell cycle progression, cERalpha is not able to induce ER-regulated genes.<br />
Despite evidence that in some systems that estrogen can have short-term rapid signaling events, we do not find that expression<br />
of cERalpha increases short-term signaling in C4-12 cells. We are currently using a rhodopsin-tagged ER which is in the<br />
plasma membrane to determine if membrane association is critical for short-term signaling, <strong>and</strong> also whether cERalpha can<br />
increase short-term estrogen signaling in MCF-7 cells that overexpress HER2.<br />
DTIC<br />
Cancer; Cells (Biology); Estrogens; Mammary Gl<strong>and</strong>s; Membranes; Receptors (Physiology)<br />
20040111556 Scripps Research Inst., La Jolla, CA<br />
Endothelial Cell-Targeted Adenoviral Vector for Suppressing Breast Malignancies<br />
Huang, Shuang; Apr. 2004; 6 pp.; In English<br />
Contract(s)/Grant(s): DAMD17-02-1-0561<br />
Report No.(s): AD-A425596; No Copyright; Avail: CASI; A02, Hardcopy<br />
The survival, growth <strong>and</strong> metastasis of solid tumors including breast cancer depends on the formation of new blood<br />
vessels to provide tumors with nutrients <strong>and</strong> oxygen, a process called angiogenesis. In vitro <strong>and</strong> in vivo experimental models<br />
indicate that suppressing angiogenesis can also suppress solid tumors. However, the success of this approach largely depends<br />
on whether sufficient amounts of therapeutic agents can be delivered to tumor-associated endothelial cells without causing<br />
toxic effects to other tissues/cells. Our proposal is designed to develop an endothelial cell-targeted adenoviral vector <strong>and</strong> to<br />
use the targeted vector to express high levels of anticancer therapeutic genes in the sites of angiogenenic tumors specifically<br />
<strong>and</strong> efficiently.<br />
DTIC<br />
Cancer; Mammary Gl<strong>and</strong>s<br />
20040111557 Tufts Univ., Boston, MA<br />
Do Perturbed Epithelial-Mesenchymal Interactions Drive Early Stages of Carcinogenesis<br />
Sonnenschein, Carlos; Apr. 2004; 16 pp.; In English<br />
Contract(s)/Grant(s): DAMD17-02-1-0595<br />
Report No.(s): AD-A425598; No Copyright; Avail: CASI; A03, Hardcopy<br />
This research project had three specific tasks. The first was to determine which tissue is the target of the chemical<br />
carcinogen N-nitrosomethylurea in the rat mammary gl<strong>and</strong>. This task was scheduled to occupy the first 18 months of support.<br />
The second task included screening <strong>and</strong> counting lesions <strong>and</strong> performing morphometric data analysis of whole mounts<br />
(branching pattern, relative abundance of the different ductal <strong>and</strong> alveolar structures). These studies aimed to identify the<br />
changes occurring between the time of exposure <strong>and</strong> the appearance of neoplasias. We also planned to analyze BrdU<br />
incorporation, <strong>and</strong> identify changes in components of the extracellular matrix. Finally, during years two <strong>and</strong> three we were<br />
supposed to explore the specific roles of hyaluronan <strong>and</strong> emmprin, two molecules that are enriched in tumors <strong>and</strong> involved<br />
in tumor-stromal cell interactions as mediators of neoplastic initiation <strong>and</strong> progression.<br />
DTIC<br />
Carcinogens; Epithelium<br />
20040111558 Texas Univ., Houston, TX<br />
A Novel Apoptotic Molecule Bok for the Treatment of Breast Cancer<br />
Bartholomeusz, Geoffrey A.; Mar. 2004; 11 pp.; In English<br />
Contract(s)/Grant(s): DAMD17-02-1-0448<br />
Report No.(s): AD-A425599; No Copyright; Avail: CASI; A03, Hardcopy<br />
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