Growth Suppression and Therapy Sensitization of Breast Cancer
Abstract
The goal of this project is to provide a rationale and pre-clinical evaluation of p53-based approaches to growth suppression and therapy sensitization of breast cancer, including combination approaches using p53 gene therapy in combination with chemotherapy or DNA repair inhibitors. The scope of the third years work was (1) to continue to evaluate how the c-Jun and p53 pathways interact to affect DNA repair, apoptosis, and the cellular response to chemotherapy, (2) to study how retinoids affect cisplatin adduct formation in specific regulatory regions of the genome, and (3) to set up an in vivo model for breast cancer metastasis to evaluate p53 combination approaches. We observed that inhibition of c-Jun N terminal phosphorylation inhibits cisplatin-induced expression of GADD45, and enhances p53 mediated induction of bax and apoptosis, suggesting that GADD45 may provide a target for new therapeutics that collaborate with p53. With regard to retinoid induced cisplatin adduct formation on the RARBeta promoter, we have shown that a region encompassing the TATA box and RARE become preferentially targeted by cisplatin following retinoid treatment. We have set up an in vivo model for breast cancer metastasis and are presently testing the efficacy of p53 plus doxorubicin therapy in inhibiting metastasis.
Document Details
- Document Type
- Technical Report
- Publication Date
- Jul 01, 1999
- Accession Number
- ADB258619
Entities
People
- Ruth A. Gjerset