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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 | Assessment of reduced models for the detection of modal interaction through rotor stator contacts显示文摘 | Alain Batailly Mathias Legrand Patrice Cartraud Christophe Pierre | 2010 | Journal of Sound and Vibration2010，329，： | 1 |
| 3 | Noniterative stable transmission/reflection method for lowloss material complex permittivity determination显示文摘 | Abdel Hakim Boughriet Christian Legrand Alain Chapoton | | 0，，1： | 1 |
| 4 | Numerical-Experimental Confrontation in the Simulation of Tool/Abradable Material Interaction显示文摘 | Alain Bataily Marion Cuny Mathias Legrand | | 0，，： | 1 |
| 5 | Biomarkers of oxidative stress: an analytical approach显示文摘 | Patrice Thérond Dominique Bonnefont-Rousselot Anne Davit-Spraul Marc Conti Alain Legrand | 2000 | Current Opinion in Clinical Nutrition and Metabolic Care2000，，5： | 1 |
| 6 | Full three-dimensional investigation of structural contact interactions in turbomachines显示文摘 | Mathias Legrand Alain Batailly Beno?t Magnain Patrice Cartraud Christophe Pierre | 2012 | Journal of Sound and Vibration2012，，11： | 1 |
| 7 | Human sperm quality and lipid content after migration into normal ovulatory human cervical mucus containing low numbers of leukocytes显示文摘这研究的目的是调查一种关系是否在颈的粘液和精子质量和类脂化合物在移植以后满足的正常 ovulatory 在白血球的低数字的存在之间存在。实时、能动、词法上正常的精子,电脑辅助的精子分析(房屋) 估计的运动参数,和流动 cytometry 测量的导致 ionophore 的 acrosome 反应的百分比在移植前后被决定。有紫外察觉的高效的液体层析被用来测量精子类脂化合物内容,包括各种各样的 diacyl 亚种。在 solubilized 粘液样品发现的白血球的数字用一个 haemocytometric 方法被数。总的来说,在颈的粘液样品的白血球的存在显著地没影响精子活动性和形态学,精子运动学的参数,或在鞘磷脂或胆固醇的精子内容。在移植以后,相反,在各种各样的精子 diacyls 和导致的 acrosome 反应的水平的减少少些显著地在比在粘液样品包含 104 个白血球没有的粘液样品或稀罕白血球被读而导致的 acrosome 反应的水平更高。现在的数据建议在正常 ovulatory 发现颈的粘液的白血球的底层能影响精子类脂化合物 remodelling/capacitation 的过程。 | Nozha Chakroun-Feki Patrice Therond Martine Couturier Florence Eustache Gerard Limea Alain Legrand Pierre Jouannet Jacques Auger | 2009 | Asian Journal of Andrology2009，11，3： | 1 |
| 8 | Metformin decreases intracellular production of reactive oxygen species in aortic endothelial cells显示文摘 | Nadjat Ouslimani Jacqueline Peynet Dominique Bonnefont-Rousselot Patrice Thérond Alain Legrand Jean-Louis Beaudeux | 2005 | Metabolism2005，，6： | 1 |
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