Modulation of apoptosis by the cyclin-dependent kinase inhibitor p27
Previously studies on p27, cyclin kinase inhibitors, have been shown that p27 related to cell proliferation and differentiation. However, The experiment result from the study group of Stuart J. Shankland suggested that p27 played a double sward role in cell programmed death. p27-/- cells could lead to decrease CDK2 activity.
The apoptosis was not detected in serum-starved transfected p27 –/– cells transfected with the p27 plasmid while detected in nontransfected cells.p27 mutant plasmid transfected cells does not bind CDK2 and GFP, also, no cell programmed death was detected.
TUNEL method has been used during this study, the staining was detected in antisense oligonucleotides (to p27) transfected cells. WB analysis showed that,CDK2 activity was increased in p27-/- mesangial cells and p27-/- fibroblasts in contrast with p27+/+ cells. the activity of CDK2 was remained increase at 6h and 18h after growth factor deprivation in p27-/-cells compared with p27+/+ cells, and CDK2 remained on protein levels in this experiment.
Quantitation of Screening Libraries was detected. In p27 –/– and p27 +/+ cells, cyclin E–CDK2 and cyclin A–CDK2 activity were increased. However, in p27 –/– mesangial cells, cyclin A–CDK2 activity, but not cyclinE–CDK2 activity, remained increased after growth factor deprivation.
All in all, this study suggested that p27 has two biological functions, preventing cell death and accelerating proliferation. The function of p27 was different under certain condition.
Considering the etiology and preventing arterial events are necessary in additional clinical trials. It is required to determine whether prolonged administration at lower doses could lead to disease stabilization with minimal toxicity or whether combination therapy could be useful.
Conclution: Screening Library, at the dose and schedule administered in the trial, is ineffective in metastatic renal cancer. In addition to the diarrhea observed in phase I studies, Walter also observed a higher incidence of asthenia and serious vascular thrombotic events than expected.
Related References:
Modulation of apoptosis by the cyclin-dependent kinase inhibitor p27
Walter M etc. Flavopiridol, A Novel Cyclin-Dependent Kinase Inhibitor,in Metastatic Renal Cancer: A University of Chicago PhaseII Consortium Study. J Clin Oncol 18:371-375,2000
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The apoptosis was not detected in serum-starved transfected p27 –/– cells transfected with the p27 plasmid while detected in nontransfected cells.p27 mutant plasmid transfected cells does not bind CDK2 and GFP, also, no cell programmed death was detected.
TUNEL method has been used during this study, the staining was detected in antisense oligonucleotides (to p27) transfected cells. WB analysis showed that,CDK2 activity was increased in p27-/- mesangial cells and p27-/- fibroblasts in contrast with p27+/+ cells. the activity of CDK2 was remained increase at 6h and 18h after growth factor deprivation in p27-/-cells compared with p27+/+ cells, and CDK2 remained on protein levels in this experiment.
Quantitation of Screening Libraries was detected. In p27 –/– and p27 +/+ cells, cyclin E–CDK2 and cyclin A–CDK2 activity were increased. However, in p27 –/– mesangial cells, cyclin A–CDK2 activity, but not cyclinE–CDK2 activity, remained increased after growth factor deprivation.
All in all, this study suggested that p27 has two biological functions, preventing cell death and accelerating proliferation. The function of p27 was different under certain condition.
Considering the etiology and preventing arterial events are necessary in additional clinical trials. It is required to determine whether prolonged administration at lower doses could lead to disease stabilization with minimal toxicity or whether combination therapy could be useful.
Conclution: Screening Library, at the dose and schedule administered in the trial, is ineffective in metastatic renal cancer. In addition to the diarrhea observed in phase I studies, Walter also observed a higher incidence of asthenia and serious vascular thrombotic events than expected.
Related References:
Modulation of apoptosis by the cyclin-dependent kinase inhibitor p27
Walter M etc. Flavopiridol, A Novel Cyclin-Dependent Kinase Inhibitor,in Metastatic Renal Cancer: A University of Chicago PhaseII Consortium Study. J Clin Oncol 18:371-375,2000
Related Posts
Review: p57Kip2, CDKs inhibitor, regulates cell cycle exit, differentiation, and migration of Embryonic Cerebral Cortical Precursors
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