A Novel Molecular Target for Breast Cancer Prevention and Treatment
Abstract
TR3 is an orphan member of the steroid/thyroid/retinoid receptor superfamily and is known to induce apoptosis of cancer cells. We have investigated the mechanism of TR3-mediated apoptosis in breast cancer cells. Our results demonstrate that TR3 exerts its apoptotic effect in breast cancer by translocating from the nucleus to mitochondria in response to apoptotic retinoids. We have also identified a new apoptotic retinoid MMOO2 that effectively induces TR3 mitochondrial targeting and apoptosis of breast cancer cells. In studying the mechanism by which TR3 migrates from the nucleus to the cytoplasm, we found that the migration of TR3 from the nucleus to the cytoplasm requires RXR through their heterodimerization. We also observed that RXR contains a nuclear export sequence that is required for its cytoplasmic localization and is regulated by RXR ligands. Furthermore, we discovered that TR3 can physically interacts with Bcl-2 and that Bcl-2 acts as a mitochondrial receptor of TR3 and is required for apoptotic effect of TR3 in breast cancer cells. Our results not only enhance our understanding of the molecular mechanism by which TR3 exerts its apoptotic effect in breast cancer cells but also provide novel approaches to induce apoptosis of Bcl-2-expressing breast cancer cells.
Document Details
- Document Type
- Technical Report
- Publication Date
- Jun 01, 2002
- Accession Number
- ADA408737
Entities
People
- Xiao-kun Zhang
Organizations
- Sanford Burnham Prebys Medical Discovery Institute