Role of Early Growth Response-1 (Egr-1) Gene in Radiation-Induced Apoptosis of Prostate Cancer Cells
Abstract
Our previous studies suggested that Egr-l is required for the growth-inhibitory and apoptotic response to ionizing radiation in the prostate cancer cell line pC-3 that lacks wild-type p53 functional protein. The effect of Egr-l was mediated through the upregulation of TNF-a protein. These results underscore the need to formally study the functional relevance of EGR-l expression in radiation treated prostate cancer cells. It is hypothesized that radiation induces EDR-l protein expression in prostatic carcinoma cells leading to the upregulation of TNF-a protein resulting in apoptosis and call 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 pf3 (DU-145) background. B. Determine the basal and radiation-inducible expression levels of Egr-l and its target gene TNF-r 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 Sgr-l, pS3 and TNp-a expression levels and ganomic Bgr-l mutations in untreated prostatic tumor specimens. After the first year of the granting period, the SI obtained NIH funding that had certain overlapping specific aims. Modified specific aims were approved by the grants Officer and a new statement of work was developed for the remaining granting period.
Document Details
- Document Type
- Technical Report
- Publication Date
- May 01, 2001
- Accession Number
- ADA398097
Entities
People
- Mansoor M. Ahmed
Organizations
- University of Kentucky