Differential Activation of p53 Target Genes in Breast Cancer
Abstract
A significant percentage of breast tumors have been shown to be resistant to apoptotic stimuli. This resistance has been correlated with a decreased expression of the proapoptotic protein bax. A major regulator of bax expression is the tumor suppressor p53. When compared to alternate target genes data suggest that the bax gene is differentially regulated by p53. Our goal is to understand the mechanism by which p53 selectively regulates the transcription of the proapoptotic bax gene. We have identified the minimal p53 responsive element in the human bax promoter, and have found it to be unique in that it consists of three p53 half-sites instead of the typical two. In addition, this minimal element appears to bind with sequence specificity to at least two factors in addition to p53. One of these factors is the transcription factor Spi which appears to contribute significantly to the basal activity of the bax promoter. The other, Factor X (as yet unidentified) binds to sequences within the p53 response element that confer transcriptional repression in the absence of p53, suggesting that Factor X may posess potent oncogenic properties through its ability to effectively compete p53 for binding to the bax promoter.
Document Details
- Document Type
- Technical Report
- Publication Date
- Jun 01, 2000
- Accession Number
- ADB261617
Entities
People
- Edward Thornborrow
- James Manfredi
Organizations
- Icahn School of Medicine at Mount Sinai