NASA Scientific and Technical Aerospace Reports

20040111575 Colorado Univ., Denver, CO
Role of Nuclear Receptor Coregulators in Hormone Resistant Breast Cancer
Nitao, Lisa; Horowitz, Kathryn B.; Sep. 2003; 74 pp.; In English; Original contains color illustrations
Contract(s)/Grant(s): DAMD17-99-1-9145
Report No.(s): AD-A425637; No Copyright; Avail: CASI; A04, Hardcopy
We propose that coregulatory proteins influence the direction of transcription by antagonist-occupied steroid receptors.
We screened for such proteins and identified three cDNA fragments encoding peptides that interact with antagonist- bound
PRs. The aims were to clone complete cDNAs; define the role of the unknown proteins on receptor activity; and determine
the role of the unknown proteins in hormone dependency of breast cancers. Major findings: We have focused on one novel
cDNA fragment, designated ORF#93. We cloned the full-length cDNA; localized the gene to chromosome l5q23.l; expressed
the full-length protein; defined its tissue distribution; and determined that it is cytoplasmic. ORF#93 doesn’t appear to have
a ligand-specific effect on PR transcription, but it does have general transcriptional effects. Prom mammalian two-hybrid and
GST pull-down assays, we’ve determined that ORF#93 interacts with hsp9O and that this is influenced by the presence of PR
and its ligands. It’s possible that ORF#93 functions to regulate key events in the formation of nascent PR, cytoplasmic
chaperone interactions and translocation into the nucleus. If so, ORF#93 may play a key role in bringing PR to associate with
cytoplasmic molecules with which PR would otherwise not interact.
DTIC
Cancer; Deoxyribonucleic Acid; Hormones; Mammary Glands; Nuclear Medicine; Receptors (Physiology)
20040111576 Texas Univ., Houston, TX
Tumor Specific Regulation of C-CAM Cell Adhesion Molecule in Prostate Cancer Carcinogenesis
Lin, Sue-Hwa; Mar. 2004; 52 pp.; In English; Original contains color illustrations
Contract(s)/Grant(s): DAMD17-98-1-8465
Report No.(s): AD-A425638; No Copyright; Avail: CASI; A04, Hardcopy
Down-regulation of carcinoembryonic antigen- related cell adhesion molecule (CEACAM1) tumor suppressor gene
expression is common in several malignancies including prostate. The mechanism that mediates this down-regulation is not
known. We propose to elucidate the mechanism of loss of CEACAM1 tumor suppressor expression in prostate cancer. We
found that down-regulation of CEACAM1 expression in prostate tumors is mainly due to transcriptional down-regulation of
CEACAM1 gene. We have identified two transcription factors, i. e. AP-2 and androgen receptor, that are involved in the upregulation
of CEACAM1 gene expression and one transcription repressor, i.e. Sp2, that specifically down-regulates
CEACAM1 promoter activity in tumor cells. The identification of Sp2 as a transcriptional suppressor of CEACAM1 gene is
a novel finding. We found that Sp2 represses CEACAM1 gene expression by recruiting histone deacetylase activity to the
CEACAM1 promoter. Thus, loss of CEACAM1 tumor suppressor gene expression in prostate cancer is due to aberrant
chromatin acetylation. Results from this study will allow us to better understand the regulation of CEACAM1 gene during
tumorigenesis and this may lead to design new therapy strategies to alter tumor progression or to implement early detection
and prevention strategies.
DTIC
Adhesion; Cancer; Carcinogens; Cells (Biology); Prostate Gland; Tumors
20040111577 South Carolina Univ., Columbia, SC
Dietary Seaweed and Early Breast Cancer: A Randomized Trial
Teas, Jane; May 2004; 69 pp.; In English
Contract(s)/Grant(s): DAMD17-98-1-8207
Report No.(s): AD-A425639; No Copyright; Avail: CASI; A04, Hardcopy
The purpose of this research is to investigate whether eating brown seaweed (Undaria pinnatifida) can influence breast
cancer risk. Brown seaweeds are popular in Japan, where the incidence of breast cancer is about 116 the rate of that reported
for American women. In several animal studies of diet and cancer, adding seaweed to the normal diet resulted in longer healthy
lives. In particular, we will examine cell-cell adhesion and gene expression associated with the consumption of dietary
seaweeds by women who are healthy and women who have breast cancer. We will use commercially available seaweed. These
seaweeds are commonly found in health food stores. To date, progress has been limited by the lack of approval from HSRRB
(Proposal Log Number BC972552, HSRRB Log Number A-8050), with modifications. Modifications were submitted August
26, 2003. Final approval has not yet been granted. However, when this grant was first awarded in 1999 to the University of
Massachusetts, we did a preliminary study to assess potential toxicity of dietary seaweed. The first paper on iodine content
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