Role of Early Growth Response-1 (Egr 1) Gene in Radiation-Induced Apoptosis of Prostate Cancer Cells
Abstract
Our previous studies in prostate cancer cells suggested that Egr-l is required for the growth-inhibitory end apostolic response to ionizing radiation in the prostate cancer cell line PC-3 which lacks wild-type p53 functional protein. The effect of Egr-l is mediated through the upregulation of TNF-a protein.. These results underscore the need to formally study the functional relevance of EDR-l expression in radiation treated prostate cancer cells. It is hypothesized that radiation induces EGR-l protein expression in prostatic carcinoma cells leading to the upregulation of TNF-a protein resulting in apoptosis and cell death. To test this hypothesis the following specific aims are proposed: A. Determine the functional and regulatory role of Egr-l in radiation- inducible apoptosis using prostate cancer cell lines exhibiting a wild-type (LNCaP) and a mutant p53 (DU-l45) background. B. Determine the besal and radiation-inducible expression levels of Egr-l and its target gene TNF-a protein as a function of radiation. Data obtained on Egr-l and its target genes will be compared to those corresponding to clonogenic survival, growth inhibition and apoptosis profiles. In this way the functional role of Egr-l in radiation treated prostate cancer cells can be elucidated. To translate these results in a clinical perspective, we will also analyze Egr-l, p53 and TNF-a expression levels and genomic Egr-l mutations in untreated prostatic tumor specimens.
Document Details
- Document Type
- Technical Report
- Publication Date
- Aug 01, 1999
- Accession Number
- ADA380406
Entities
People
- Mansoor M. Ahmed
Organizations
- University of Kentucky