Head and Neck Cancer Clinical Trial
Official title:
Novel Protein Regulator of Tumor Suppressor ARF & NF-κB
RATIONALE: Studying proteins in head and neck cancer cells in the laboratory may help
doctors learn more about changes that occur in DNA and identify biomarkers related to
cancer.
PURPOSE: This laboratory study is looking at proteins in head and neck cancer cells.
OBJECTIVES:
- Define the function and mechanism of LZAP in regulating ARF.
- Determine the mechanism and biological consequences of LZAP inhibition of NF-κB.
- Determine if LZAP has tumor suppressor activity by conditional targeting of LZAP in
mice.
OUTLINE: Using molecular laboratory techniques, this study examines the biochemical
mechanisms by which LZAP activates transcriptional, tumor suppressive activity (both
p53-dependent and p53-independent) of ARF and inhibits transcriptional, tumorigenic activity
of NF-kB. LZAP regulation of newly identified ARF activities, such as S-phase delay and
ARF-mediated B23 degradation are also evaluated. LZAP's tumor suppressive activity is
assessed in vivo using a conditional knockout vector to target LZAP in mice and to observe
for spontaneous and induced tumor formation. Laboratory analyses used to determine study
endpoints include standard recombinant DNA, recombinant protein expression and purification,
cell culture and transfection, cell labeling, reporter assays, flow cytometry, yeast-two
hybrid, immunoprecipitation, immunoblotting, immunofluorescence, TUNEL assay, ELISA assay,
Southern blotting, and protein and gene expression.
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