NASA Scientific and Technical Aerospace Reports

20040111717 Beth Israel Deaconess Medical Center, Boston, MA
The Non-Classical Secretion of Thioredoxin from Breast Cancer Cells
Chuck, Steven L.; Jun. 2003; 26 pp.; In English
Contract(s)/Grant(s): DAMD17-01-1-0150
Report No.(s): AD-A425885; No Copyright; Avail: CASI; A03, Hardcopy
Thioredoxin is a small protein with a catalytic site for redox reactions that is involved in several physiologic and
pathophysiologic processes in humans. A ubiquitous cytosolic protein, thioredoxin also is secreted by some types of cells
including cells derived from leukemia, lung, colon, and breast cancers. Extracellular thioredoxin acts as an autocrine growth
factor and can potentiate the action of other cytokines on these tumor cell lines. The novel pathway by which thioredoxin is
secreted has not been elucidated. Our specific aims are to: identify the amino acid sequence within thioredoxin that directs its
secretion from cells, and to identify the cellular gene products that secrete thioredoxin from breast cancer cells. We aim to
develop a molecular view of the non-classical process by which thioredoxin is secreted. Armed with a thorough understanding
of this export process, it may be possible to slow the growth of breast cancers in humans in an entirely new way by inhibiting
the release of thioredoxin.
DTIC
Cancer; Mammary Glands; Proteins; Secretions
20040111721 Medical Univ. of South Carolina, Charleston, SC
The Bioconcentration Hypothesis: Potential Role of Transporter in Breast Ductules
Karnaky, Karl J., Jr; Oct. 2002; 46 pp.; In English; Original contains color illustrations
Contract(s)/Grant(s): DAMD17-98-1-8125
Report No.(s): AD-A425890; No Copyright; Avail: CASI; A03, Hardcopy
Hope for prevention of breast cancer arises from international breast cancer rate variation, which suggests potentially
modifiable environmental determinants of the disease. We used immunocytochemical and Western blot methods to localize
two membrane xenobiotic transporter, MRP1 and MRP2. MRP2 is located at the apical membrane of epithelial cells and
excretes anionic hydrophobic substrates, such as 17 beta- estrogen glucuronide, antioxidants, and toxic molecules into lumen
of the kidney, liver, and gut. In isolated and tissue cultured breast ductules, MRP2 is located predominantly in the apical region
of luminal epithelial cells and thus might bioconcentrate toxic substrates into sealed, non-flushed lumens. In a comparison
epithelium, Caco2 cells in culture, MRP2 is localized at the apical membrane only and is detected as bands at 60 and 190 kDa
in blots, but in breast tissue cultures MRP2 is detected only at 60 kDa. MRP1 transports anionic hydrophobic molecules across
the basolateral side of epithelial cells into the connective tissue. In isolated and tissue cultured breast ductules, MRP1 is
localized in the cytoplasm, as is typical for numerous epithelial cells and is detected as a band at 190 kDa. Thus, overall
transport of toxins to, and bioconcentration in, breast ductile lumens may be determined by a balance between these-two
transporters.
DTIC
Antioxidants; Cancer; Carcinogens; Epithelium; Mammary Glands; Membranes; Transporter
20040111724 Colorado State Univ., Fort Collins, CO
Identification of Novel Genes Affected by Gamma Irradiation Using a Gene-Trapped Library of Human Mammary
Epithelial Cells
Malone, Jennifer L.; Ullrich, Robert; Apr. 2004; 47 pp.; In English; Original contains color illustrations
Contract(s)/Grant(s): DAMD17-02-1-0349
Report No.(s): AD-A425893; No Copyright; Avail: CASI; A03, Hardcopy
We propose that the expression of several unknown genes is affected by gamma radiation. Abnormal expression of these
genes may be one of the steps in breast carcinogenesis induced by radiation. We plan to establish an assay that will allow us
to screen for breast cells that contains a single mutation by gene trapping. We will be able to detect changes in the expression
of a gene upon treatment with different doses of radiation. These radiation-responsive genes will be identified through the rapid
amplification of cDNA ends procedure and sequenced. Cells that are affected by radiation will be isolated and analyzed to see
if the changes can lead to transformation of the normal breast epithelial cell into a neoplastic cell. This assay may prove to
be a powerful tool in the identification of novel genes that are affected by gamma irradiation in the early stages of breast cancer
progression. The 3’RACE protocol has recently been completed and thirty one genes potential genes were sequenced. Of
these, six candidate genes were found. The include: human creatine kinase gene, human androgen receptor, human DORA
reverse strand protein 1 (DREVl), human eukaryotic translation elongation factor 1 beta 2 (EEFlB2), human ribosomal protein
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