Novel Transcriptional Interactions Between the Estrogen and Retinoic Acid Receptors in Human Breast Cancer Cells
Abstract
The purpose of this research is to investigate the specific mechanisms by which transcriptional pathways may become more responsive to retinoids in cells that express estrogen receptor (ER alpha). Understanding how the steroid hormone receptors interact to control transcription and inhibit growth of cancer cells will suggest directions for the use of retinoids, or may provide the foundation for target-oriented therapies in breast cancer. To determine which region of the ER is required for retinoid sensitivity, several deletion mutants of ER were subcloned into a retroviral vector containing an internal ribosomal entry site (IRES) and green fluorescent protein (GFP). Viral producers were generated and target ER-negative cells were infected with vims containing ER-deletion mutant, ER-wild-type or the empty retroviral control vector. Transduced cell lines were analyzed by flow cytometry for expression of GFP and by Northern for expression of the bicistronic ER-GFP RNA species. The ER-deletion mutants have yet to be analyzed but thus far, the ER-transduced cell lines are growth inhibited by retinoids and give a greater than 100 fold induction on a betaRARE compared to the retroviral control. These results indicate that the restored response to RA is due to the presence of ERalpha only. Indeed, the mRNA level of ERalpha does not differ significantly in the ER-positive and ER-negative cell lines observed.
Document Details
- Document Type
- Technical Report
- Publication Date
- Jun 01, 1999
- Accession Number
- ADB258933
Entities
People
- Caroline Rousseau
Organizations
- McGill University