SXR: A Target for Breast Cancer Prevention and Treatment
Abstract
Anti-estrogens such as tamoxifen are important therapeutic agents in the treatment and chemoprevention of breast cancers. Other compounds such as phytoestrogens, fatty acid amides and retinold X receptor (RxR) agonists are also effective against breast cancer in cell lines and in animal models. Because these compounds are unrelated it has not been appreciated that they might act through a common mechanism. These compounds all share the ability to activate a heterodimer of the steroid and xenobiotic receptor (SxR) and RXR. Our hypothesis is that SXR serves as a common molecular target for some of the anti- proliferative effects of these compounds and that activation of SXR is itself anti-proliferative. We have analyzed mRNA from breast cancer cell lines treated with SXR activators by micorarray, and have validated some of the putative SXR target genes found using quantitative real time RT-PCR. We have also analyzed the mechanism by which SXR activation stops cell proliferation using assays for apoptosis and necrosis. Our preliminary results indicate that SXR activators may be inducing caspase-dependent apoptosis to stop the apparent cell proliferation. Further experiments are underway to study SXR activator-induced apoptosis and link this effect back to the induced SXR target genes found by microarray.
Document Details
- Document Type
- Technical Report
- Publication Date
- Apr 01, 2004
- Accession Number
- ADA425590
Entities
People
- Bruce Blumberg
Organizations
- University of California, Irvine