Abstract LB-9: DNA binding distinguishes wild-type and mutant p53 activity

Abstract

Abstract Cell cycle regulation is a function of several regulatory genes such as cyclin G, p21, etc. controlled by p53. Several other genes such as pcna, puma, noxa involved in DNA repair and apoptotic pathways are also coordinated by p53. It is thus understandable that mutations in p53 could result in de-regulation of cell cycle progression, DNA repair, apoptosis, etc. Any imbalance in the above mentioned processes normally culminates in cancer. Our present focus of study is breast cancer where the cells harbor either wild-type or mutant p53. Progression of cancer in cell lines with wild-type p53 indicates a different regulatory switch/pathway responsible for the establishment of this disease. In an effort to understand the functional effect of both wild-type and mutant p53, we have done p53 DNA binding with nuclear extracts from several breast cancer cell lines using two assays. The DNA sequences being considered as target for p53 binding are from genes involved in cell cycle regulatory pathways, DNA repair, apoptosis and p53 regulation. We have observed differences in binding of p53 to some of these gene sequences. Cell lines with wild-type p53 and functional estrogen receptor (ER) bind more to the promoter for pcna and cyclin G than cell lines with mutant p53. The binding to the promoter of the puma gene is more similar between cell lines with mutant and wild-type p53 than the other genes analyzed. We anticipate a certain trend in DNA binding based on the functional status of p53 and its interaction with other proteins such as ER. This trend of p53 binding to different gene sequences may be utilized to better understand the causes of breast cancer, its subsequent progression as well as for designing treatment protocols. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr LB-9.