Mechanism of Retinoid Response in Human Breast Cancer
Abstract
We have investigated the anti-cancer effects of retinoids, the natural and synthetic vitamin A derivatives, in breast cancer cells. Our data demonstrate that retinoids can effectively inhibit growth of breast cancer cells. The growth inhibitory effect of retinoids is mediated by their induction of retinoic acid receptor beta (RAR-beta) expression, expression, in addition to their suppression of mitogenic effect of estrogen receptor and inhibition of AP-1 activity. Expression of RAR-beta inhibits growth of breast cancer cells by promoting their apoptosis. Our study also show that retinoid activity in breast cancer cells is regulated by BAG-1, a recently identified cell survival gene that interacts with Bcl-2, providing a possible molecular basis for interaction between retinoid and apoptosis signaling. In studying regulation of RAR-beta expression, we demonstrate that two retinoid signaling pathways, i.e., the RXR-dependent pathway and the RAR-dependent pathway, can induce RAR-beta expression and growth inhibition. In addition, we have found that lack of COUP-TF expression is mainly responsible for loss of RAR-beta expression in retinoid-resistant breast cancer cells. These results largely enhance our understanding of the mechanism of retinoid action in breast cancer cells and also point to a possibility of restoring or enhancing retinoid activity in breast cancer cells.
Document Details
- Document Type
- Technical Report
- Publication Date
- Oct 01, 1999
- Accession Number
- ADA385837
Entities
People
- Zhang Xiao-kun
Organizations
- Sanford Burnham Prebys Medical Discovery Institute