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| 1 | c-Fos overexpression increases the proliferation of human hepatocytes by stabilizing nuclear Cyclin D1显示文摘AIM: To investigate the effect of stable c-Fos overexpression on immortalized human hepatocyte (IHH) proliferation. METHODS: IHHs stably transfected with c-Fos (IHH-Fos) or an empty vector (IHH-C) were grown in medium supplemented with 1% serum or stimulated with 10% serum. Cell proliferation was assessed by cell counts, 3H-thymidine uptake and fl ow cytometry analyses. The levels of cell cycle regulatory proteins (Cyclin D1, E, A) cyclin dependent kinases (cdk) cdk2, cdk4, cdk6, and their inhibitors p15, p16, p21, p27, to- tal and phosphorylated GSK-3β and epidermal growth factor receptor (EGF-R) were assayed by Western blot- ting. Analysis of Cyclin D1 mRNA levels was performed by reverse transcription-polymerase chain reaction and real-time polymerase chain reaction (PCR) analysis. Stability of Cyclin D1 was studied by cycloheximide blockade experiments. RESULTS: Stable c-Fos overexpression increased cell proliferation under low serum conditions and resulted in a two-fold increase in [3H]-thymidine incorpora- tion following serum addition. Cell cycle analysis by fl ow cytometry showed that c-Fos accelerated the cell cycle kinetics. Following serum stimulation, Cyclin D1 was more abundantly expressed in c-Fos overexpressing cells. Cyclin D1 accumulation did not result from increased transcriptional activation, but from nuclear stabilization. Overexpression of c-Fos correlated with higher nuclear levels of inactive phosphorylated GSK- 3β, a kinase involved in Cyclin D1 degradation and higher levels of EGF-R mRNA, and EGF-R protein compared to IHH-C both in serum starved, and in serum stimulated cells. Abrogation of EGF-R signalling in IHH- Fos by treatment with AG1478, a specif ic EGF-R tyrosine kinase inhibitor, prevented the phosphorylation of GSK-3β induced by serum stimulation and decreased Cyclin D1 stability in the nucleus. CONCLUSION: Our results clearly indicate a positive role for c-Fos in cell cycle regulation in hepatocytes. Importantly, we delineate a new mechanism by which c-Fos could contribute to hepatocarcinogenesis through stabilization of Cyclin D1 within the nucleus, evoking a new feature to c-Fos implication in hepatocellular carcinoma. | Meryem Güller Kahina Toualbi-Abed Agnès Legrand Laurence Michel Alain Mauviel Dominique Bernuau Fanny Daniel | 2008 | World Journal of Gastroenterology2008,14,41: | 6 |
| 2 | Adult biphenotypic acute leukaemia: an entity with poor prognosis which is related to unfavourable cytogenetics and P-glycoprotein over-expression显示文摘 | Legrand O Perrot JY Simonin G | 1998 | BrJ Haematol1998,100,1: | 1 |
| 3 | Laparoscopic treatment of nonparasitic liver cysts: adequate selection of patients and surgical technique显示文摘 | Gigot J F Legrand M Hubens G | 1996 | World J Surg1996,20,: | 1 |
| 4 | Combined hydroxypropyl-β-cyclodextrin and poly (alkylcyanoacrylate) nanoparticles intended for oral administration of saquinavir显示文摘 | BOUDAD H LEGRAND P LEBAS G | 2001 | Int J Pharm2001,218,12: | 1 |
| 5 | Adult biphenotypic acute leukemia; an entity with poor prognosis which is related to unfavourable cytogenetics and pglycoprotein over expression显示文摘 | Legrand O Perrot J Y Simonin G | 1998 | Br J Haematol1998,100,1: | 1 |
| 6 | Adult biphenotypie acute leukemia: an entity with poor prognosis which is related to unfavourable cytogenetics and P-glycoprotein over-expression显示文摘 | LEGRAND O PERROT JY SIMONIN G | 1998 | Br J Haematol1998,100,1: | 1 |
| 7 | Adult biphenotypic acute leukemia:an entity with poor progrosis which is related to un- favourable cytogenetics and P-glycoprotein over-expression显示文摘 | Legrand O Perror JY Simonin G | 2012 | Bri J Haematol2012,100,1: | 1 |
| 8 | Both P-gp and MRP contribute to drug resistance in AML显示文摘 | Legrand O Simonin G Zittoun R | 1998 | Leukemia1998,12,8: | 1 |
| 9 | Comparison of MDR1, MRP and LRP expression with in vitro drug sensitivity in vivo response to treatment in fresh blast cells from abult acute myeloid leukemia patients显示文摘 | Legrand O Simonin G Zittoun R | 1997 | Blood1997,90,: | 1 |
| 10 | Determination of twelve antiretroviral agents in human plasma sample using reversed-phase high -performance liquid chromatograph显示文摘 | Aymard G Legrand M Trichereau N | 2000 | J Chromatograph B2000,744,: | 1 |
| 11 | Combined hydroxypropyl-β-cyclodextrin and poly ( alkyl cyanoacrylate)nanoparticles intended for oral administration of saquinavir 显示文摘 | Boudad H Legrand P Lebas G | 2001 | Int J Pharm2001,218,12: | 1 |
| 12 | Thermal impact of SaharanDust over land,part I:simulation显示文摘 | Cautenet G Legrand M Cautenet S | 1992 | Meteorology1992,31,: | 1 |
| 13 | Laparoscopic treatment of nonparasitic liver cysts : adequate selection of patients and surgi- cal technique 显示文摘 | Gigot JF Legrand M Hubens G | 1996 | World J Surg1996,20,5: | 1 |
| 14 | Laparoscopic treatment of nonparasitic liver cysts:adequate selection of patients and surgical technique显示文摘 | Gigot JF Legrand M Hubens G | 1996 | World J Surg1996,20,5: | 1 |
| 15 | A quasi-monte carlo integration method applied to the computation of the Pollaczek integral显示文摘 | Legrand X Xemard A Fleury G | 2008 | IEEE Transactions on Power Delivery2008,23,3: | 1 |
| 16 | Laparoscopic treatment of nonparasitic liver cysts:adequate selection of patients and syrgical technique显示文摘 | Legrand M ralld M Hubens G | 1996 | World J surg1996,20,1: | 1 |
| 17 | A raman and infared study of a new carbonate green rust obtained by electrochemical way显示文摘 | Legrand L Sagon G | 2001 | Corrosion Science2001,34,4: | 1 |
| 18 | Long-term women-reported quality of life after radical eystectomy and orthotopie ileal neobladder reeonstruetion显示文摘 | Rouanne M Legrand G Neuzillet Y | 2014 | Ann Surg Oneol2014,21,4: | 1 |
| 19 | Characterization of a hospital outbreak of imipenem-resistant Acinetobacter baumannii by phenotypic and genotypic typing methods显示文摘 | Tankovie J Legrand P De Gatines G | 1994 | J Clin Microbiol1994,32,11: | 1 |
| 20 | Allelopathic effect of Prymnesium parvum on a natural plankton community显示文摘 | Fistarol G O Legrand C Graneli E | 2003 | Marine Ecology-Progress Series2003,255,: | 1 |