THE EFFECTS OF BREFELDIN A (BFA) ON CELL CYCLE PROGRESSION INVOLVING THE MODULATION OF THE RETINOBLASTOMA PROTEIN (pRB) IN PC-3 PROSTATE CANCER CELLS
| Autor: | Sensuke Konno, John A. Mordente, Camille Mallouh, Hiroshi Tazaki, Yuping Chen, Joseph M. Wu |
|---|---|
| Rok vydání: | 1998 |
| Předmět: |
Male
medicine.medical_specialty Time Factors Urology Cell Cyclopentanes Retinoblastoma Protein S Phase chemistry.chemical_compound Cyclin D1 Internal medicine Tumor Cells Cultured medicine Humans Phosphorylation Protein Synthesis Inhibitors Brefeldin A biology Cell growth Cyclin-dependent kinase 2 G1 Phase Retinoblastoma protein Prostatic Neoplasms Cell cycle Cyclin-Dependent Kinases Cell biology Endocrinology medicine.anatomical_structure chemistry Cell culture biology.protein Cell Division |
| Zdroj: | Journal of Urology. 159:275-279 |
| ISSN: | 1527-3792 0022-5347 |
| Popis: | To investigate the effects of brefelding A (BFA) on the growth of the androgen-independent human prostate cancer PC-3 cells, focusing on cell cycle regulation.BFA is a fungal macrocyclic lactone with an antiviral activity. PC-3 cells were cultured with various concentrations of BFA for indicated times and cell growth was monitored at each time point. Cell cycle analysis was performed to explore the mechanism of BFA-induced growth inhibition. To further investigate the cell cycle regulation, cell cycle-controlling factors, such as the retinoblastoma gene product (pRB) and its regulatory components cdk2, cdk4, and cyclin D1, were analyzed by Western immunoblots.BFA was a potent growth inhibitor at a concentration of 30 ng./ml., resulting in a70% reduction in cell number at 3 days. Cell cycle analysis revealed a cell arrest in the G1 to S phase transition. Western blots further showed that BFA induced dephosphorylation of pRB accompanied by down regulation of cdk2, cdk4, and cyclin D1 expression. The extended pRB dephosphorylation in control cell lysates was also observed by the addition of BFA-treated lysates, but was prevented by the inclusion of phosphatase inhibitors in assay mixtures.These results suggest that BFA may be a potent cell cycle modulator, which post-translationally regulates pRB phosphorylation possibly by down-regulating cdk2, cdk4, and cyclin D1 and/or by up-regulating a phosphatase(s) capable of dephosphorylating pRB. Thus, BFA-induced growth inhibition in PC-3 cells appears to be at least partially due to the modulation of a pRB-mediated growth pathway. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|