Regulation of IAP (Inhibitor of Apoptosis) Gene Expression by the p53 Tumor Suppressor Protein
Abstract
The goal of the work proposed in this application, which has just completed Year 1, was to analyze the ability of the p53 tumor suppressor protein to repress the anti-apoptotic genes survivin and cIAP-2. In particular, we proposed to clone and characterize the cIAP-2 promoter, and to use DNA footprinting on the survivin promoter to look for p53 association in vivo. This has been accomplished. Additionally, we proposed to determine the mechanism whereby the survivin gene is over-expressed in breast tumor cells relative to non-transformed breast cells (MCF-IOF). We have determined that the survivin promoter is E2F-responsive; this transcription factor is de-regulated in many breast carcinomas, as well as other tumor types. We show that the E2F site in the survivin promoter is responsible for the enhanced expression of survivin in breast carcinomas versus non-transformed breast epithelial cells. All of the goals for Year 1 have been accomplished; part of this work has been published in the manuscript presented in the Appendix (Bao et al., 2002); the majority is in preparation for submission. We are moving forward to Task 2 (years 12.36), the generation of a replication-selective adenovirus that has the ElA gene driven by the survivin promoter.
Document Details
- Document Type
- Technical Report
- Publication Date
- May 01, 2003
- Accession Number
- ADA417659
Entities
People
- Maureen E. Murphy
Organizations
- Fox Chase Cancer Center