Tumor Suppression and Sensitization to Taxol Induced Apoptosis of E1A In Breast Cancer Cells

摘要

The purpose of this project is to study the molecular mechanisms underlying E1A's proapoptotic effect and anti-tumor activity and to dissect the functional domains of El A that are critical for its antitumor activity. Because a phase I E1A gene therapy protocol for human breast and ovarian cancers was completed and a phase II clinical trial is undergoing, we also plan to develop an alternative E1A mutant construct to maximize El A therapeutic effects while minimizing its potential side-effects for cancer gene therapy. In trying to understand the mechanism underlying E1A's antitumor activity, we have found that E1A downregulated VEGF expression both in vitro and in vivo, and mapped the domains required for this activity. We have also identified additional new target genes that were critically involved in El A-mediated chemosensitization. Also, we have been trying to identify other molecules that may be regulated by E1A via the genomic and proteomic approaches. These studies can provide useful information for us to better understand the molecular functions of E1A, and hopefully we can use this knowledge to better design a mutant E1A construct for cancer gene therapy in the future.