NASA Scientific and Technical Aerospace Reports
NASA Scientific and Technical Aerospace Reports
NASA Scientific and Technical Aerospace Reports
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<strong>and</strong> loss of heterozygosity occurs in TSC tumors. Tuberin <strong>and</strong>/or hamartin appear to be involved in multiple cellular pathways:<br />
vesicular trafficking, signaling via the small GTPase Rap 1, cell cycle regulation, steroid hormone function, cell adhesion via<br />
the small GTPase Rho, <strong>and</strong> signaling via ribosomal protein S6 <strong>and</strong> MTOR, which regulate protein synthesis <strong>and</strong> cell growth.<br />
The in vivo importance of these different activities <strong>and</strong> their contributions to human TSC are not yet entirely understood.<br />
DTIC<br />
Convulsions; Genes; Steroids<br />
20040111667 Washington Univ., Seattle, WA<br />
Clinical <strong>and</strong> Molecular Consequences of NF1 Microdeletion<br />
Stephens, Karen; May 2004; 33 pp.; In English<br />
Contract(s)/Grant(s): DAMD17-03-1-0203<br />
Report No.(s): AD-A425784; No Copyright; Avail: CASI; A03, Hardcopy<br />
Skin neurofibromas are the most common tumors of patients with neurofibromatosis type 1 (NF1), yet we know very little<br />
about how they develop. We are studying NF1 subjects with microdeletions because they are predisposed to large numbers<br />
of neurofibromas. We propose that deletion of NF1 gene <strong>and</strong> one of the 15 adjacent genes favors the development of skin<br />
neurofibromas, <strong>and</strong> possibly also other tumors. We are currently evaluating NF1 subjects to identify those with deletions <strong>and</strong><br />
determine when <strong>and</strong> what kind of tumors <strong>and</strong> other clinical features they develop. We have developed new competitive PCR<br />
assays to rapidly screen for deletion patients. Later in the study we, will look for specific genetic changes in skin<br />
neurofibromas of patients with NF1 deletions to provide insight into how they develop. We propose to employ new <strong>and</strong><br />
powerful technology from the Human Genome Project to confirm or disprove the presence of a t<strong>and</strong>em NF1-like gene. If<br />
present, this gene may contribute in some unknown way to making the disease more or less severe. Therefore, identifying a<br />
tumor modelling gene <strong>and</strong> the possible t<strong>and</strong>em NF1-like gene will help us underst<strong>and</strong> tumorigenesis in these patients.<br />
DTIC<br />
Cells (Biology); Genetics<br />
20040111668 California Univ., Berkeley, CA<br />
TGF-B Regulation of the Mammary Radiation Response<br />
Pajares, Maria J.; Dec. 2003; 32 pp.; In English<br />
Contract(s)/Grant(s): DAMD17-01-1-0291<br />
Report No.(s): AD-A425786; No Copyright; Avail: CASI; A03, Hardcopy<br />
Transforming growth factor beta 1 (TGF-beta 1) orchestrates the response of different cell types to injury via regulation<br />
of proliferation, apoptosis <strong>and</strong> ECM composition. Previously we discovered that TGF beta 1 is rapidly activated in mammary<br />
gl<strong>and</strong> following radiation. Because TGF- beta 1 is implicated in regulation of proliferation <strong>and</strong> apoptosis, we investigated<br />
whether the activation of TGF-beta 1 contributes to the cell fate decisions in response to radiation. We found that<br />
radiation-induced apoptosis <strong>and</strong> cycle cell arrest are absent in adult mammary epithelium <strong>and</strong> embryonic liver <strong>and</strong> epidermis<br />
when TGF-beta 1 is compromised. Since p53 abundance <strong>and</strong> activity is thought to dictate apoptotic cellular responses to<br />
radiation, we examined the p53 response. We found that both chronic <strong>and</strong> transient depletion of TGF-beta 1 compromise the<br />
p53 response. In order to study the mechanism by which TGF-beta 1 affects the p53 response we cultured mammary epithelial<br />
cells (MECs). This in vitro model present TGF-beta 1 dependent radiation response similar to that seen in vivo. Treatment of<br />
MECs with TGF-beta 1 restored both p53 response <strong>and</strong> caspase 3 cleavage in the heterozygote cultures. We propose that<br />
TGF-beta 1 is a key regulator of epithelial genomic integrity since its loss impairs activation of p53 resulting in reduced<br />
apoptosis <strong>and</strong> cell cycle arrest.<br />
DTIC<br />
Mammary Gl<strong>and</strong>s<br />
20040111670 Albany Medical Coll., NY<br />
Breast Cancer Research Undergraduate Summer Training Program<br />
Andersen, Thomas; Jun. 2004; 34 pp.; In English<br />
Contract(s)/Grant(s): DAMD17-01-1-0121<br />
Report No.(s): AD-A425791; No Copyright; Avail: CASI; A03, Hardcopy<br />
It is important to recruit a cadre of talented investigators whose careers are dedicated to studies of prevention, treatment,<br />
<strong>and</strong> early detection of breast cancer. By investing in young people before they make career choices, <strong>and</strong> by providing them<br />
with first-h<strong>and</strong> experience in modern breast cancer research (BCR) laboratories, we are finding that several of these young<br />
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