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West Virginia IDeA Network of Biomedical
Research Excellence |
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Featured Researcher: Dr. Albert Magro,
Fairmont State College, Studies Mechanisms of Breast Cancer
Development
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 WV-INBRE
participants, Drs. Albert Magro of Fairmont State College (right)
and Michael Miller of West Virginia University (left), are currently
investigating the role of arachidonate lipoxygenase in the induction
of apoptosis in human breast cancer cells (MCF-7). Experiments
tested the hypothesis that the blocking of cellular lipoxygenases in
MCF-7 cells inhibits growth, induces apoptosis, and modulates the
transcriptional expression of the pro-apoptotic gene Bax-α and the
anti-apoptotic gene Bcl-2. They have demonstrated that inhibition of
arachidonate 5, 8, and 12 lipoxygenases induces massive apoptosis as
measured by nuclear fragmentation DNA laddering, which are classical
manifestations of apoptosis. The detection of soluble cytoplasmic
DNA histone complexes resulting from apoptotic nucleosomes, that are
tightly bound with core histones and appear in the cytosol before
the plasma membrane disintegrates, also indicates that the
inhibition of lipoxygenases induces apoptosis in MCF-7 cells.
Preliminary RT-PCR data indicate that the induction of apoptosis is
accompanied by a decrease in the steady-state expression of Bcl-2
with an increase in the expression of Bax-α. An interesting aspect
of this study is that MCF- 7 cells, which are deficient in caspase
3, still manifest classical apoptosis that is believed to be caspase-dependent.
Furthermore, the broad caspase inhibitor, Z-VAD FMK, prevents
apoptosis induced by lipoxygenase inhibition in these cells. This
was unexpected and the investigators are currently pursuing the
interesting question of which effector caspases are activated during
the apoptotic process. These molecular studies between arachidonic
acid metabolism and apoptosis in breast cancer cells raise the
possibility for identification of novel molecular targets for
cancer, chemoprevention, and treatment. Dr. Magro presented the
results of this research at the Cold Spring Harbor Laboratory
Meeting entitled “Programmed Cell Death”, September 17-23, 2003.
In addition to their research on breast cancer, Drs. Magro and
Miller were awarded a $20,000 grant from the NASA WV-EPSCoR
College-University Collaboration Program, for a study entitled
“Analysis of Human Epithelial Cells and Corticol Neurons for
Susceptibility to Apoptosis Induced by Hypoxia”.
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