A Novel Knock-Out Animal Model to Analyze Transcriptional Signaling by p53 Tumor Suppressor Protein in Breast Cancer
Abstract
Two important transcriptional targets of p53 tumor suppressor protein are genes encoding the Proliferating Cell Nuclear Antigen (PCNA) and p21/WAF1/Cip1. PCNA is a necessary component of DNA replication and DNA repair machinery. p21/WAF1/Cip1 is a cyclin-dependent kinase (cdk) inhibitor which can interact with PCNA to modulate the balance of DNA repair versus replication. We hypothesize that correct ratio of PCNA and p21 proteins is crucial for normal regulation of DNA repair and cell cycle control, and hence, disregulation of PCNA and p21 transcription in response to genomic damage is an important aspect of breast cancer formation. To test this hypothesis in vivo, we are developing a mouse model where p53 signaling specifically to the PCNA and p21 gene transcription is disrupted. Toward this goal, we are characterizing p53 interaction sites on mouse p21 and PCNA gene promoters (from a series of BAC clones isolated with the help of Poswell Park Cancer Institute Microarray and Genomics Facility). This mouse model will enable testing the relevance of specific transcriptional signaling by p53 to mammary oncogenesis, identification of new therapeutic targets, and analyzing the role of specific p53 transcriptional targets in modulating responses to chemotherapeutic drugs and radiation therapy.
Document Details
- Document Type
- Technical Report
- Publication Date
- May 01, 2002
- Accession Number
- ADB282132
Entities
People
- Gokul M. Das
Organizations
- University of Texas Health Science Center at San Antonio