Overexpression of p21waf1/cip1 arrests the growth of chicken embryo fibroblasts that overexpress E2F1.
P21waf1/cip1 is a potent inhibitor of cell cycle progression and can inhibit the growth of both normal cells and cells transformed by a number of oncogenes. However, the ability of p21waf1/cip1 to inhibit the growth of cells that overexpress the transcriptional transactivator E2F1 is controversial: it has been reported both that E2F1 can and cannot overcome the block in the cell cycle induced by p21waf1/cip1. To avoid the complications that arise when such experiments are done with permanent cell lines, we tested the effects of overexpressing p21waf/cip1 and E2F1 in primary chicken embryo fibroblasts. In this system very high levels of E2F1 overexpression cause considerable apoptosis; however, the surviving cells still overexpress E2F1. These cells are transformed and their growth is blocked by overexpression of p21waf1/cip1.
Givol
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ABL-Basic Research Program, NCI-Frederick Cancer Research and Development Center, Maryland 21702-1201, USA.
Givol
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Hughes
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D000818:Animals; D017209:Apoptosis / Q000235:genetics; D002352:Carrier Proteins; D018797:Cell Cycle Proteins; D002455:Cell Division / Q000235:genetics*; D002461:Cell Line, Transformed; D002642:Chick Embryo; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016213:Cyclins / Q000235:genetics*; D004268:DNA-Binding Proteins; D050684:E2F Transcription Factors; D050687:E2F1 Transcription Factor; D005347:Fibroblasts / Q000166:cytology / Q000378:metabolism; D016193:G1 Phase / Q000235:genetics; D005822:Genetic Vectors; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D056465:Retinoblastoma-Binding Protein 1; D012190:Retroviridae / Q000235:genetics; D014157:Transcription Factors / Q000235:genetics*
D002352:Carrier Proteins; D018797:Cell Cycle Proteins; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016213:Cyclins; D004268:DNA-Binding Proteins; D050684:E2F Transcription Factors; D050687:E2F1 Transcription Factor; D019253:Proto-Oncogene Proteins c-bcl-2; D056465:Retinoblastoma-Binding Protein 1; D014157:Transcription Factors