Involvement of mitogen-activated protein kinases and p21Waf1 in hydroxyurea-induced G1 arrest and senescence of McA-RH7777 rat hepatoma cell line
| Autor: | Joo-In Park, Dae-Cheol Kim, Jin-Sook Jeong, Seung-Hee Hong, Bum-Sik Hong, Mee-Sook Rho, Ho-Sun Jun, Soe-Hee Rha |
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| Rok vydání: | 2004 |
| Předmět: |
Cyclin-Dependent Kinase Inhibitor p21
MAPK/ERK pathway p38 mitogen-activated protein kinases Clinical Biochemistry Antineoplastic Agents Cell Cycle Proteins Biochemistry Liver Neoplasms Experimental Cell Line Tumor Animals Hydroxyurea Phosphorylation Molecular Biology Cellular Senescence Cell Proliferation biology Cell growth Kinase Tumor Suppressor Proteins G1 Phase Cell cycle Molecular biology Rats Up-Regulation Cell culture Mitogen-activated protein kinase biology.protein Molecular Medicine Mitogen-Activated Protein Kinases Tumor Suppressor Protein p53 Signal transduction Cyclin-Dependent Kinase Inhibitor p27 |
| Zdroj: | Experimental & Molecular Medicine. 36:493-498 |
| ISSN: | 2092-6413 |
| Popis: | Hydroxyurea is commonly used to treat hematologic disorders and some type of solid tumors, but the mechanism for its therapeutic effect is not clearly known. In this study, we examined the effect of hydroxyurea on rat hepatoma McA-RH7777 cells, specifically, on the role of mitogen-activated protein (MAP) kinase signal transduction pathways and p21(Waf1), p27(Kip1) and p53. Rat hepatoma McA-RH7777 cells treated with hydroxyurea for 7 days, caused the inhibition of cell growth in a dose-dependent manner. But, this growth inhibition was not caused by necrosis or apoptosis but instead was associated with cell senescence-like change as evidenced by senescence associated-beta-galactosidase staining, and cells arrest at G1 phase of cell cycle. Phosphorylation of MAP kinases, such as ERK, JNK, and p38, was found to be decreased after treatment of cells with hydroxyurea. But, the expression of p21(Waf1) was increased, while p27(Kip1) and p53 were not detected in hydroxyurea treated rat hepatoma cells. Hydroxyurea treatment induced G1 arrest and a senescence-like changes in rat hepatoma McA-RH7777 cells may be the likely results of signal disruption of MAP kinases (ERK, JNK, and p38 MAP kinase) and p21(Waf1) over-expression. |
| Databáze: | OpenAIRE |
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