NASA Scientific and Technical Aerospace Reports

Evidence show that TNFa is able to regulate b-catenin through IkappaB kinase complex. This complex is normally involved
in inactivating inhibitor, IkappaB which sequesters NFkappaB in the cytoplasm. The second part of this project shows that
NEkappaB signaling is independent of TKK regulation of b-catenin. Wnt signaling is not the only way b-catenin is regulated.
Cytokine induced decrease in b-catenin signaling activity is not due to b- catenin degradation but rather, to its re-distribution.
This study confirms that there is an active’ fraction of b-catenin present within the nucleus is responsible for its signaling
activity and both TNFa and ectodysplasin reduce or redistribute that fraction.
DTIC
Cancer; Cells (Biology); Mammary Glands
20040111728 Manitoba Univ., Winnipeg, Manitoba
Markers of Increased Risk in Pre-Invasive Breast Cancer
Mandal, Soma; Watson, Peter; Feb. 2004; 20 pp.; In English
Contract(s)/Grant(s): DAMD17-00-1-0318
Report No.(s): AD-A425897; No Copyright; Avail: CASI; A03, Hardcopy
The understanding of the risk of recurrence and progression of breast cancer, particularly, from a pre- invasive lesion is
evasive and challenging. Our goal has been to identify changes in early breast cancer using techniques to profile global gene
expression. In previous work, we have employed cDNA array techniques to identify relatively small changes in gene
expression between low and high risk pre- invasive cancer. We have therefore optimized the alternative SAGE (serial analysis
of gene expression) technique to also apply to this problem and compare with our cDNA results. We have tested SAGE
initially in a small pilot experiment, using transfected cell lines that differ in their expression of the psoriasin gene, that is
commonly overexpressed in pre-invasive cancer. A pilot experiment using two SAGE libraries showed that differences can be
detected and larger experiment is now underway. Clones with inserts have been screened by PCR and agarose gel analysis and
are now being sequenced. We anticipate that this experiment will establish the capability of this assay to detect differential
gene expression and lay the foundation for its application to pre-invasive tumor samples, and may identify gene that are
overexpressed in pre- invasive disease.
DTIC
Cancer; Genes; Mammary Glands; Markers; Risk
20040111729 Dana Farber Cancer Inst., Boston, MA
Regulation of the Activity of AIB1 an Estrogen Receptor Coactivator by Growth Factor Signals
Torres-Arzayus, Maria; Jul. 2003; 13 pp.; In English
Contract(s)/Grant(s): DAMD17-01-1-0223
Report No.(s): AD-A425898; No Copyright; Avail: CASI; A03, Hardcopy
The AIB1 protein is a member of a coactivator family that potentiates the transcriptional activity of the nuclear hormone
receptors. AIB1, is amplified in certain breast and ovarian cancers and has been suggested that AIB1 plays a causative role
in breast cancer development. Our lab recently identified AIB1 as a target of the MAPK signaling pathway (Font de Mora and
Brown, Mol Cell Biol 20:5041, 2000). Based on these findings, we propose that the phosphorylation of AIB1 by MAPK may
represent part of the molecular mechanism that integrates signals from steroid hormones and growth factors. In order to
identify the sites of AIB1 that are phosphorylated by MAPK, seven potential phosphorylation sites were targeted for point
mutations and or deletions. Previously we showed by an In vitro phosphorylation assay by (Erk2) that three out of the seven
putative phosphorylation sites tested were most likely to be the specific MAPK phosphorylation sites. In order to investigate
the physiological relevance of the AIB1 phosphorylation sites, we subcloned all mutants into GAL4DBD vector. We found
that those mutants that showed low phosphorytation in vitro, gave the lowest transactivation levels when tested in vivo. In
addition we were able to differentiate the sub-cellular localization of AIB1 after phosphorylation by performing transient
transfection in COS cells using a constitutively active MAPK vector and a kinase inhibitor vector and further on performing
immunofluorescence.
DTIC
Cancer; Estrogens; Mammary Glands
20040111730 New Jersey Medical School, New Brunswick, NJ
Inhibition of Breast Cancer-Induced Angiogenesis by a Diverged Homeobox Gene
Gorski, David H.; May 2004; 91 pp.; In English; Original contains color illustrations
Contract(s)/Grant(s): DAMD17-03-1-0292
Report No.(s): AD-A425899; No Copyright; Avail: CASI; A05, Hardcopy
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