Mechanism of Retinoid Response in Human Breast Cancer
Abstract
Natural retinoids (vitamin A derivatives) and their synthetic analogs can prevent the development of breast cancer in animals. Several retinoids are now being evaluated for their ability to prevent breast cancer recurrence in patients at risk. Unfortunately, most retinoids evaluated so far do not prevent the appearance of more malignant breast cancers that have lost their dependence on estrogens for growth, consistent with in vitro observation that the anti-cancer effects of retinoic acid (RA) are mainly seen in estrogen-dependent breast cancer cell lines. Previously, we have shown that the anti-cancer effects of RA in breast cancer cells are mainly mediated by RAR beta, and that RAR beta is not expressed in estrogen independent breast cancer cell lines. In the past funding year, we convincingly demonstrated that RXR-selective retinoids, through a new mechanism of action, can induce RAR beta expression and growth inhibition in estrogen-independent breast cancer cells, revealing a novel growth inhibition pathway. In addition, we observed that retinoid activities in breast cancer cells is regulated by BAG-1, a recently identified cell survival gene that can interact with BCL-2, providing a possible molecular basis for interaction between retinoid and apoptosis signalings.
Document Details
- Document Type
- Technical Report
- Publication Date
- Oct 01, 1998
- Accession Number
- ADA366638
Entities
People
- Xiao-kun Zhang
Organizations
- Sanford Burnham Prebys Medical Discovery Institute