Changes in E2F binding after phenylbutyrate-induced differentiation of Caco-2 colon cancer cells
| Autor: | Q M, Wang, R, Feinman, F, Kashanchi, J M, Houghton, G P, Studzinski, L E, Harrison |
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| Rok vydání: | 2000 |
| Předmět: |
Time Factors
Cell Cycle Proteins Protein Serine-Threonine Kinases S Phase Proto-Oncogene Proteins CDC2-CDC28 Kinases Humans Tumor Suppressor Proteins Cell Cycle Cyclin-Dependent Kinase 2 G1 Phase Cyclin-Dependent Kinase 4 Cell Differentiation Cyclin-Dependent Kinase 6 Alkaline Phosphatase Phenylbutyrates Cyclin-Dependent Kinases E2F Transcription Factors DNA-Binding Proteins Kinetics Caco-2 Cells Carrier Proteins Microtubule-Associated Proteins Transcription Factor DP1 Cell Division Cyclin-Dependent Kinase Inhibitor p27 Retinoblastoma-Binding Protein 1 Transcription Factors |
| Zdroj: | Clinical cancer research : an official journal of the American Association for Cancer Research. 6(7) |
| ISSN: | 1078-0432 |
| Popis: | Differentiation agents use existing cellular systems to induce neoplastic cells to regain a normal phenotype and/or to cause growth arrest and therefore may offer novel chemotherapeutic approaches to treating solid tumors. In this study, we demonstrate in Caco-2 colon cancer cells that the differentiation agent phenylbutyrate (PB) causes a decrease in viable cells, an increase in cell differentiation, and a G1-S-phase block. The mechanism of this last effect is related to a PB-induced increase in p27Kip1, leading to a decrease in the activity of cyclin-dependent kinase 2 (CDK2), a positive regulator of the G1-S-phase cell cycle transition. Consistent with the decreased CDK2 kinase activity, we also observed a decrease in the phosphorylation state of the retinoblastoma protein after PB treatment. This was associated with increased binding and consequent inactivation of E2F, a transactivator of genes that regulate the G1 to S phase cell cycle transition. These data suggest that the differentiation agent PB inhibits tumor growth by limiting the availability of active E2F, with a subsequent G1-S-phase block. Additional studies should show whether PB is a clinically effective therapeutic agent against colorectal cancer. |
| Databáze: | OpenAIRE |
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