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| 1 | Involvement of extracellular signal-regulated kinase/mitogenactivated protein kinase pathway in multidrug resistance induced by HBx in hepatoma cell line显示文摘AIM: To investigate the molecular mechanism of the influence of HBx protein on multidrug resistance associated genes: multidrug resistance 1 (MDR-1), multidrug related protein (MRP-1), lung resistance related protein (LRP) in hepatoma cells and the potential role of extracellular signal-regulated kinase/mitogen-activated protein kinase (ERK/MAPK) pathway in this process.METHODS: A cell model stably expressing the HBx protein was established by liposome-mediated transfection of HBx gene into HepG2 cell line. The expression of multidrug resistance associated genes and proteins was detected by RT-PCR and Western blot. AnnexinV-FITC/PI assay was used to confirm the multidrug resistance (MDR) phenotype of transfected cells by fluorescence cytometry (FACS). The ERK/MAPK pathway activation was measured by Western blot through comparing the ratio of phosphorylation of ERK/MAPK to total ERK/MAPK protein. After treated with the ERK/MAPK pathway inhibitor U0126, the HBx-expressing cells were harvested. Then RT-PCR, Western blot and FACS were used to analyze the alterations in the expression of multidrug resistance associated genes and the MDR phenotype after exposure.RESULTS: Compared with the control group, the transfected cells showed a higher expression of MDR associated genes and proteins. Marked elevations in MDR-1 (64.3%), MRP-1 (87.5%) and LRP (90.8%) were observed in the transfected cells (P<0.05). RT-PCR revealed that the over-expression of MDR associated proteins was due to amplification of such genes (MDR1 2.9 fold, MRP1 1.67 fold, LRP1.95 fold).Furthermore, we found that the ERK/MAPK activity was remarkably high in the HBx-expressing cells. The activation of ERK/MAPK, as measured by the ratio of phosphorylated ERK bands normalized to the total ERK bands, was increased by 2.3-fold in HBx-transfected cells compared with cells transfected with the empty vector. After treated with the ERK/MAPK pathway inhibitor, the level of MDR associated genes and proteins in the transfected cells decreased to some extent. Compared with controls, a significant decrease in MDR-1 mRNA (53.3%), MRP-1 mRNA (59.7%) as well as LRP mRNA (56.4%) was observed in the UO126 treated transfected cells after 12 h. Western blot also demonstrated that the protein expression of these MDR associated genes slightly reduced after treated with U0126 for 12 h (MDR-1 40.1%, MRP-1 29.4%, LRP35.7%). This change was accompanied with the rise of cell apoptosis ratio confirmed by Annexin V-PI detection. The apoptosis index of UO126treated cells increased by 1.28 fold, compared with that of transfected cells. Obviously, the MDR phenotype of these cells was obviously related with increased activities of the ERK/MAPK pathway.CONCLUSION: HBx protein might be one of the causes for the occurrence of MDR in HCC, and ERK/MAPK pathway might be involved in this change. | JianGuan Xiao-PingChen HongZhu Shun-FengLuo BinCao LeiDing | 2004 | World Journal of Gastroenterology2004，10，23： | 15 |
| 2 | Tomato fruit cuticular waxes andtheir effects on transpiration barrier properties:functional characterizationof a mutant deficient in a very-long-chain fatty acidβ-ketoacyl-CoA syn-thase显示文摘 | VOGG G FISCHER S LEIDE J | 2004 | Journal of Experment Botany2004，55，： | 1 |
| 3 | Cleavage and inaction of human CI inhibitor by the human leukocyte proteinase, proteinase显示文摘 | Leid RW Ballieux BE Van-der-heijden I | 1993 | Eur J Immunol1993，23，11： | 1 |
| 4 | Detection of apoptosis by TUNEL assay 显示文摘 | Kyrylkova K Kyryachenko S Leid M | 2012 | Methods Mol Biol2012，887，： | 1 |
| 5 | In vitro antimicrobial studies of silver carbene complexes : activity of free and nanopar- ticle carbene formulations against clinical isolates of pathogenic bacteria 显示文摘 | Leid J G Ditto A J Knapp A | 2012 | J Antimicrob Chemother2012，67，1： | 1 |
| 6 | Hypothyroxinaemia and thyroid function after preterm birth显示文摘 | Leid G Wassenaer JH | 2004 | Semin Neonatal2004，9，1： | 1 |
| 7 | A classification of mental models of undergraduates seeking information for a course essay in history and psychology:Preliminary investigations into aligning their mental models with online thesauri显示文摘 | Cole C Lin Y Leide J | | 0，，13： | 1 |
| 8 | Bacterial biofilms on the sinus mucosa of human subjects with chronic rhinosinusitis 显示文摘 | Sanderson AR Leid JG Hunsaker D | 2006 | Laryngoscope2006，116，7： | 1 |
| 9 | The developmental pat-tern of tomato fruit wax accumulation and its impact on cuticular transpira-tion barrier properties:effects of a deficiency in aβ-Ketoacyl-Coenzyme Asynthase(LeCER6)显示文摘 | LEIDE J HILDEBRANDT U REUSSING K | 2007 | Plant Physiology2007，144，： | 1 |
| 10 | A classification of mental models of undergraduates seeking information for acourse essay in history and psychology: Preliminary investigations into aligning their mental models with online thesauri显示文摘 | Cole C Lin Y Leide J | 2007 | Journal of the American Society for Information Science and Technology2007，58，13： | 1 |
| 11 | Biofilms with fungi in chronic rhinosinusitis显示文摘 | HEALY D Y LEID J G SANDERSON A R | 2008 | Otolaryngol Head Neck Surg2008，138，： | 1 |
| 12 | Controlled user evaluations of information visualization interfaces for text retrieval: Literature review and meta- analysis显示文摘 | Julien C A Leide J E Boutheilier F | 2008 | Journal of the American Society for Information Science and Technology2008，59，6： | 1 |
| 13 | A classification of mental models of undergraduates seeking information for a course essay in history and psychology: Preliminary investigations into aligning their mental models with online thesauri 显示文摘 | Cole C Lin Yang Leide J | 2007 | Journal of the American Society for Information Science and Technology2007，58，13： | 1 |
| 14 | Deficiency in a very-long-chain fatty acidβ-ketoacyl-CoA synthase(SlCER6)of tomato impairs mi-crogametogenesis and causes floral organ fusion显示文摘 | SMIRNOVA A LEIDE J RIEDERER M | 2013 | Plant Physiology2013，161，1： | 1 |
| 15 | Abnormal spermatogenesis in RXR beta mutant mice 显示文摘 | Kastner P Mark M Leid M | 1996 | Genes Dev1996，10，1： | 1 |
| 16 | Multiplicity generates diversity in the retinoic acid signaling pathway显示文摘 | Leid M Kastner P Chambon P | 1992 | Trends Biochem Sci1992，17，10： | 1 |
| 17 | Humanleukocytes adhere to, penetrate, and respond to Staphylococcus aureus biofilms显示文摘 | Leid JG Shirtliff ME Costerton JW | 2002 | Infectlmmun2002，70，11： | 1 |
| 18 | Endothelial seeding polyeraflotoethylene femoral poplliteral bypass显示文摘 | Herring MB Leide S | 1995 | J Vasc Surg1995，11，： | 1 |
| 19 | Parasite defense mechanisms for evasion of host attack: a review显示文摘 | Leid SW Suquet CM Wakelin D | 1987 | Vet Parasitol1987，25，2： | 1 |
| 20 | Warts and all: human papillomavirus in primary immunodeficiencies 显示文摘 | Leiding J W Holland S M | 2012 | J Allergy Clin Immunol2012，130，5： | 1 |
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