Isolation and Functional Characterization of Prostate Tumor-Specific Hypoxia-Inducible Promoter/Enhancer Elements for Use in Gene Therapy

The major objective of this research project is to identify and characterize promoter/enhancer elements that can be used to specifically target the expression of therapeutic genes to hypoxic regions within prostatic tumors in vivo. We have characterized sequences present within the human TNF-alpha p...

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Bibliographic Details
Main Author: Dougherty, Shona T
Format: Report
Language:English
Subjects:
ACTIVATION
Anatomy and Physiology
CELLS(BIOLOGY)
CLONES
EPITHELIUM
GENES
Genetic Engineering and Molecular Biology
HYPOXIA
IN VIVO ANALYSIS
INDUCTION SYSTEMS
IONIZING RADIATION
ISOLATION
Medicine and Medical Research
NEOPLASMS
PANELS
PROSTATE GLAND
STIMULI
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Description
Summary:The major objective of this research project is to identify and characterize promoter/enhancer elements that can be used to specifically target the expression of therapeutic genes to hypoxic regions within prostatic tumors in vivo. We have characterized sequences present within the human TNF-alpha promoter that are responsible for both constitutive activity and induction by hypoxia. We have produced a mutated version of this promoter that exhibits substantially reduced constitutive activity in epithelial cells while retaining responsiveness to various activating stimuli including hypoxia and ionizing radiation. While lacking prostate specificity, it is hoped nevertheless that this element may prove useful in various cancer gene therapy applications. In addition, we have cloned and characterized a large panel of novel sequences that exhibit high levels of constitutive promoter activity in prostate cell lines. Finally, we have identified a number of hypoxia inducible-promoter element and are currently characterizing these with respect to their prostate specificity.