NASA Scientific and Technical Aerospace Reports

mouse to test our NY-ESO-l and Her2/neu vaccines. These recombinant L. monocytogenes-based vaccines are a potential
therapeutic strategy for breast cancer treatment.
DTIC
Cancer; Mammary Glands; Vaccines
20040111625 Pennsylvania Univ., Philadelphia, PA
The Role of Dynamin in the Regulation of Signaling by the erbB Family of Receptor Kinases
King, Megan; Lemmon, Mark; Apr. 2004; 9 pp.; In English; Original contains color illustrations
Contract(s)/Grant(s): DAMD17-02-1-0546
Report No.(s): AD-A425724; No Copyright; Avail: CASI; A02, Hardcopy
Improper regulation of the level and duration of activated erbB family growth factor receptors at the cell surface can lead
to uncontrolled cell proliferation and transformation via over-stimulation of mitogenic signaling cascades. The large GTPase
dynamin is a key regulator both of transport of receptors to the plasma membrane after receptor biosynthesis and
down-regulation of receptors via receptor- mediated endocytosis (RME), during which it is involved in the scisson of
endocytic vesicles. Disruption of RME has been shown to render the epidermal growth factor receptor (erbBl) oncogenic (1),
illustrating the importance of proper attenuation of signaling by down-regulation. This proposal addresses the mechanistic role
of the pleckstrin homology (PH) domain in dynamin function, which may provide a pharmacologic target for modulating
dynamin activity. The PH domain binds% phosphatidylinositol (4,5) bisphosphate (PI(4,5)P2) at the plasma membrane (PM),
but the role of this binding is not yet understood. The experiments detailed below address whether PI(4,5)P2 binding is
involved in targeting of dynamin to the PM, or whether phosphoinositide binding instead plays a more physical role in the
scission of endocytic vesicles, and therefore receptor downregulation.
DTIC
Biosynthesis; Cancer; Epithelium; Mammary Glands; Mitosis; Receptors (Physiology)
20040111626 Mount Sinai Hospital, Toronto, Ontario
Characterization of the Interactions of BRCA1 and Protein Phosphatase 1
Hendry, Sherry L.; May 2004; 12 pp.; In English; Original contains color illustrations
Contract(s)/Grant(s): DAMD17-02-1-0496
Report No.(s): AD-A425725; No Copyright; Avail: CASI; A03, Hardcopy
The breast cancer susceptibility gene BRCAl is mutated in many cases of familial breast and ovarian cancer. BRCAl is
phosphorylated from S to M phase of the cell cycle, as well as in response to DNA damage, and a hypophosphorylated form
of BRCAl is found at the centrosome during M phase of the cell cycle. Phosphorylation may play an important role in the
regulation of BRCAl function. We have performed a yeast two- hybrid study in order to identify proteins that interact with
exonll of BRCAl. Among the proteins identified in the screen was Protein Phosphatase 1 (PPl), a serine threonine phosphatase.
PPl and BRCAl co-immunoprecipitate both in vitro and in vivo, and a GST pull down assay has identified the region within
BRCAl that is involved in the interaction. Colocalization studies of the two proteins provide further evidence for an interaction
of BRCAl and PPl within the nucleus of the cell. Mutational analysis has identified 2 sequence alterations in PPl alpha, and
expression analysis of PPl mRNA has been performed. Studies also show that PPl alpha dephosphorylates BRCAl in vitro.
The interaction of PPl and BRCAl represents a potentially significant interaction that could have an affect on the function of
BRCAl.
DTIC
Cancer; Genes; Mammary Glands; Proteins
20040111627 Nebraska Univ., Omaha, NE
Role of Estrogen Metabolism in the Initiation of Prostate Cancer: Biomarkers of Susceptibility and Early Detection
Cavalieri, Ercole L.; May 2004; 7 pp.; In English
Contract(s)/Grant(s): DAMD17-02-1-0660
Report No.(s): AD-A425726; No Copyright; Avail: CASI; A02, Hardcopy
Treatment of Noble rats with testosterone plus estradiol (E2) induces prostate carcinomas. We think that estrogens initiate
prostate cancer by reaction of catechol estrogen-3,4-quinone (CE-3,4-Q) metabolites with DNA. Formation of depurinating
adducts by CE-3,4-Q, which generate apurinic sites in DNA, would be the critical event leading to mutations that initiate
prostate cancer. After treatment of rats with CE or CE-3,4-Q, CE metabolites and CE-glutathione (GSH) conjugates were
lower in regions where tumors develop and methoxyCE were higher in regions where tumors do not develop. To study the
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