NASA Scientific and Technical Aerospace Reports

20040111604 Winston-Salem State Univ., Winston-Salem, NC
A Novel Apoptosis Pathway that is Defective in Early Breast Cancer
Thorburn, Andrew M.; Phil, D.; Apr. 2004; 9 pp.; In English
Contract(s)/Grant(s): DAMD17-02-1-0612
Report No.(s): AD-A425681; No Copyright; Avail: CASI; A02, Hardcopy
This project studies a novel apoptosis pathway that is induced by the death domain of the adaptor protein FADD
(FADD-DD) . This pathway can induce apoptosis only in normal epithelial cells from the breast (or prostate) and its
inactivation may represent an early defect that arises in breast cancer. SV4O T antigen can selectively block this apoptosis
pathway. The overall goal of this project is to investigate and further understand why breast cancer cells are resistant to this
apoptosis pathway. As outlined in the previous progress report, we achieved all the goals for aim 1 and made new observations
that allow alternate approaches to address the project. Importantly we showed that mouse breast epithelial cells display the
same apoptosis response to FADD- DD. The reviewer of our previous progress report suggested that we study this response
in the absence of Sv4OT antigen since this would be more applicable to actual breast cancer. We therefore continued with our
studies as outlined in the statement of work and expanded our studies in mouse cells that allow us to avoid the use of Sv4O
T antigen. Our data show that inactivation of the p53, Rb, INK4a/ARF pathways do not explain resistance to this apoptosis.
DTIC
Apoptosis; Cancer; Defects; Mammary Glands
20040111605
Distribution of the Coenzyme M Pathway of Epoxide Metabolism Among Ethene-and Vinyl Chloride-Degrading
Mycobacterium Strains
Coleman, Nicholas V.; Spain, Jim C.; Jul. 9, 2003; 7 pp.; In English
Report No.(s): AD-A425682; No Copyright; Avail: CASI; A02, Hardcopy
An epoxyalkane:coenzyme M (CoM) transferase (EaCoMT) enzyme was recently found to be active in the aerobic vinyl
chloride (VC) and ethene assimilation pathways of Mycobacterium strain JS6O. In the present study, EaCoMT activity and
genes were investigated in 10 different mycobacteria isolated on VC or ethene from diverse environmental samples. In all
cases, epoxyethane metabolism in cell extracts was dependent on CoM, with average specific activities of EaCoMT between
380 and 2,910 nmol/min/ mg of protein, PCR with primers based on conserved regions of EaCoMT genes from
Mycobacterium strain JS6O and the propene oxidizers Xanthobacter strain Py2 and Rhodococcus strain B-276 yielded
fragments (834 bp) of EaCoMT genes from all of the VC- and ethne-assimilating isolates. The Mycobacterium EaCoMT genes
form a distinct cluster and are more closely related to the EaCoMT of Rhodococcus strain B%276 than that of Xanthobacter
strain ....... The CoM-mediated pathway of epoxide metabolism appears to be universal in alkene-assimilating mycobacteria,
possibly because of plasmid-mediated lateral gene transfer.
DTIC
Chlorides; Coenzymes; Degradation; Enzymes; Epoxy Compounds; Metabolism; Vinyl Radical
20040111606 Fox Chase Cancer Center, Philadelphia, PA
Cloning of a New Gene/s in Chromosome 17p3.2-p13.1 that Control Apoptosis
Russo, Jose; Apr. 2004; 20 pp.; In English; Original contains color illustrations
Contract(s)/Grant(s): DAMD17-02-1-0384
Report No.(s): AD-A425683; No Copyright; Avail: CASI; A03, Hardcopy
Loss of genetic material (LOH) in the chromosome 17 p13 .2 at the microsatellite marker Dl7S796 has been identified
in atypical ductal hyperplasia and in situ ductal carcinoma of the breast. Our results shown LOH at the same region in
MCF-lOF cells treated with the chemical carcinogen benz(a)pyrene (BP). Moreover, microcell-mediated transfer of an intact
copy of human chromosome 17 inhibited the tumorigenicity of BPlE and PCR-SSCP analyzes showed a restoration of the lost
material in BPlE-17-neo. These experiments suggested the presence of a tumor suppressor gene in 17pl3 .2 near the marker
Dl 7S796. We have been able to clone a fragment of the genes that could represent the last exon of a bigger peptide. The
presence of a 3’ splicing site in the putative introns and the ATTAAA region at the 3’end support this idea. The predicted amino
acid sequence does not share significant homology with any known protein supporting the idea that this could be a novel
protein. Further experiments will be done in order to clone the full-Length cDNA and to study the regulation of the expression
of this novel gene.
DTIC
Apoptosis; Cancer; Chromosomes; Cloning (Biology); Genes; Mammary Glands
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