Induction of Apoptosis in Human Breast Cancer By Adenoviral-Mediated Gene Transfer of the Transcription Factor E2F- 1.
Abstract
Breast cancer is the most common cancer occurring in American women. New therapies are needed for treatment of patients who fail standard treatments. We have sought to develop a gene therapy strategy for the treatment of breast cancer utilizing a recombinant adenovirus vector for delivery of the transcription factor E2F-1. We have previously shown that overexpression of E2F-1 can lead to the induction of apoptosis in breast carcinoma cells. We have demonstrated that E2F-1 can be expressed in the majority of cell lines tested. Iliere is a differential sensitivity to apoptosis which may be related to uptake of the adenovirus vector or due to the genetic background of the cell. Our work demonstrates that the tumor suppresserp53 is not required for apoptosis. We have studied the interaction between the retinoblastoma tumor suppresser gene and E2F-l and shown that pRE partially blocks the apoptosis induced by E2F- 1. We are beginning to study apoptotic mediators involved in this E2F-induced apoptotic process. Preliminary results demonstrate that bax is not upregulated, however, bcl-2 is markedly upregulated. We are continuing to assess other apoptotic mediators in addition to cell cycle regulatory proteins in order to befter understand the mechanism of E2F-induced apoptosis.
Document Details
- Document Type
- Technical Report
- Publication Date
- Aug 01, 1998
- Accession Number
- ADA359219
Entities
People
- Kelly K. Hunt
Organizations
- The University of Texas MD Anderson Cancer Center