Molecular Markers of Retinoid Action in Human Prostate
Abstract
Retinoic acid (RA) has been used successfully in cancer prevention and therapy. RA exerts its biological effects through retinoic acid receptors (RARs, alpha, beta, gamma) It has been reported that RARbeta plays an important role in mediating growth inhibitory actions of RA. The expression of RAR beta is lost in prostate cancer cell lines, PC-3, and DU-145, while transfection of RAR beta into PC-3 cells results in an increased sensitivity to growth inhibitory effects of RAR beta aganist. Despite the correlation between the level of RAR beta and the RA-associated growth inhibition, it remains unknown how RAR beta mediates the growth inhibitory effects of RA. This study used murine F9 wild type (Wt) and RAR beta knockout (F9 RAR beta-1-) cells as an experimental model to investigate the molecular mechanisms by which RAR beta mediates the growth inhibitory actions of RA. Our study demonstrated that p27, a cell cycle progression regulatory protein, is increased by RA in F9 Wt cells as compared to the F9 RAR beta-1- cells. In addition, RA stabilizes the protein stability of p27. Considering the striking findings that transfection of RAR% into the PC-3 cells results in an increased sensitivity to growth inhibition caused by RAR beta against, our study may lead to more efficient chemotherapy with retinoids.
Document Details
- Document Type
- Technical Report
- Publication Date
- Jun 01, 2003
- Accession Number
- ADA418424
Entities
People
- Lorraine J. Gudas
- Rong Li
Organizations
- Cornell University