靶向SPK1的RNA干扰对前列腺癌细胞Du145的影响
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摘要
研究背景:
前列腺癌是男性泌尿生殖系统常见的恶性肿瘤,近年来我国前列腺癌发病率逐渐上升,前列腺癌目前多采用雄激素全阻断为主的内分泌治疗,但多数病人在经过内分泌治疗后,常常转为非雄激素依赖性,成为激素难治性前列腺癌,出现复发或多发转移。传统的手术、放疗、化疗和激素疗法对激素难治性前列腺癌治疗效果不佳,目前国内外许多学者都在探求基因水平的调控方法和寻找治疗的新靶点,以期在前列腺癌的治疗上取得突破。
近年研究证明细胞膜鞘磷脂的衍生物包括神经酰胺(Cer)、鞘氨醇(Sp)、1-磷酸鞘氨醇(S1P)等多种代谢产物,在调节细胞增殖和凋亡的动态平衡中起着关键的作用。而鞘氨醇激酶(SPK)是维持细胞内上述物质平衡的重要限速酶,也是细胞增殖及存活的重要调控因子。鞘氨醇激酶信号通路与细胞的凋亡、生长、增殖密切相关,SPK1是其主要功能酶。Cer和Sp是细胞增殖的负调控因子,能够抑制细胞生长、促进细胞凋亡,S1P则刺激细胞生长、抑制细胞凋亡。SPK1磷酸化Sp生成S1P,S1P通过细胞内外作用机制调节细胞生长和凋亡。对SPK1进行调控,将影响细胞内Cer、Sp、S1P的水平,细胞内Cer、Sp、S1P的水平的高低,将影响细胞的生长、增殖和凋亡。
RNA干涉(RNAi)是近期发展起来的一种新的基因治疗和诊断技术,RNA干涉是指在多种生物细胞内,由双链RNA介导同源序列mRNA的特异性降解,从而导致基因沉默的现象。我们设想通过RNA干涉的方法,导致SPK1基因沉默,进而抑制SPK1的表达,调节神经酰胺、鞘氨醇、1-磷酸鞘氨醇在细胞内的水平,诱导非激素依赖性前列腺癌细胞的凋亡,以探讨对非激素依赖性前列腺癌细胞的基因治疗。
目的:通过检测SPK1信号分子在非激素依赖性前列腺癌细胞Du145中的表达情况,以及评价重组腺病毒Ad-H1-SPK1介导,RNA干涉Du145细胞SPK1基因,对SPK1和抗凋亡蛋白Mcl-1表达的影响;探讨重组腺病毒Ad-H1-SPK1介导,干涉SPK1对细胞凋亡的作用及可能的机制,为非激素依赖性前列腺癌细胞的基因治疗寻找新的靶点。
方法:我们选择非激素依赖性前列腺癌细胞株Du145,作为我们的实验研究对象;构建并制备了携带SPK1特异干涉序列的重组腺病毒Ad-H1-SPK1,作为介导对SPK1基因进行RNA干涉的研究工具;我们利用RT-PCR的方法,检测Du145细胞株中SPK1信号分子的表达;用腺病毒Ad-GFP作为参照,用不同滴度的腺病毒对Du145细胞进行感染,检测腺病毒对Du145的感染效率;我们用Ad-H1-SPK1感染Du-145细胞,并以不含SPK1特异干涉序列腺病毒Ad-H1作为对照,Western blot检测SPK1的表达,并用Western blot检测重要抗凋亡蛋白Mcl-1的表达,评价干涉SPK1对SPK1、Mcl-1蛋白表达的影响;用MTT的方法检测干涉SPK1,对阿霉素抑制前列腺癌细胞Du-145增殖的影响;用流式细胞仪检测细胞的凋亡情况,评价干涉SPK1对喜树碱诱导Du-145细胞凋亡的影响。
结果:我们用RT-PCR的方法,在非激素依赖性前列腺癌细胞株Du-145中检测到了SPK1信号分子的表达;我们测定腺病毒对Du-145细胞的感染效率为99.92%(MOI=100),完全可以满足后续实验的要求;用Ad-H1-SPK1感染Du-145细胞,介导对SPK1进行干涉,SPK1干涉后,SPK1、Mcl-1蛋白表达明显受到抑制,Ad-H1-SPK1+阿霉素组细胞生存率低于对照Ad-H1+阿霉素组,48小时为对照组的71.2%,72小时为对照组的61.3%:用流式细胞仪检测Du145细胞的凋亡,Ad-H1-SPK1+喜树碱组的平均细胞凋亡率58.3%,高于对照组Ad-H1+喜树碱组29.1%,经统计学处理,差异有显著性(P＜0.01)。
结论:我们的研究结果表明,SPK信号通路可以调节非激素依赖性前列腺癌细胞Du145的凋亡,靶向SPK1的RNA干扰可以抑制Du145细胞的SPK1以及重要抗凋亡蛋白Mcl-1的表达,增加阿霉素对Du145细胞增殖的抑制,增加喜树碱诱导的Du145细胞的凋亡。SPK信号通路可能为前列腺癌基因治疗提供新的靶点。
Background
Prostate cancer is one of the most common malignant tumor of the male urogenital system. In China, it' s mobidity has been rising yearly in the recent decade . Endocrine therapy of androgen blockade is the mainly treatment for prostate cancer at present. But most patients after endocrine therapy usually change into androgen-independent and become hormone refractory prostate cancer ,recurrence or metastasis .Traditional surgery, radiotherapy, chemotherapy and endocrine therapy are ineffective for hormone refractory prostate cancer. Many scholars explore at the level of gene regulation and control to the treatment of prostate cancer,and look for a new target for treatment to make a breakthrough . In recent years, studies have proved that membrane sphingomyelin derivatives include ceramide (Cer), sphingosine (Sp), sphingosine-1- phosphate (S1P) and other metabolites .They plays a key role in the dynamic equilibrium regulation of cell proliferation and apoptosis . The sphingosine kinase (SPK) is important rate-limiting enzyme to maintain the intracellular balance of these substances. It was important regulatory factors of cell proliferation and survival. The cell levels of these sphingolipid metabolites are regulated by sphingosine kinase (SPK) which phosphorylates Sp to form S1P and regulates its cellular levels. Sphingosine kinase signaling pathway are closely related with cell apoptosis, growth and proliferation.
RNA interference (RNAi) is recently developed a new gene therapy and diagnostic technology. RNA interference happen in a variety of biological cells .It is special phenomenon that double-stranded RNA mediated homologous sequence specific mRNA degradation and led to gene silencing. We envisage that RNA interference cause SPK1 gene silencing, thereby inhibiting the expression of SPK1, regulating ceramide, sphingosine-l-phosphate,sphingosine intracellular level, Induced apoptosis of hormone-independent prostate cancer cell. It was explored for hormone-independent prostate cancer gene therapy.
OBJICTIVER: SPK1 signal molecule expression were examined in the hormone-independent prostate cancer cells line Du145. SPK1 and Myeloid cell leukemia-1 (Mcl-1) expression were examined after recombinant adenovirus Ad-H1-SPK1 mediated SPK1 interference on Dul45 cell .It was discussed that SPK1 interference play role on Du145 cell apoptosis and possible mechanism. We want to look for a new target for hormone-independent prostate cancer gene therapy.
Method: The hormone-independent prostate cancer Du145 cell was selected as experimental subject. Recombinant adenovirus Ad-H1-SPK1 which carry SPK1 specific interference sequence was built and prepared, as an research tool to mediat RNA interference for SPK1 gene. RT-PCR method was used to measure SPK1 signal molecule expression on Du145. Infected efficiency of Du145 was tasted with adenovirus Ad-GFP as a reference. Adenovirus Ad-H1 which not to carry SPK1 specific interference sequence was as control. SPK1 and Mcl-1 expression was measured by Western blotting. Influence of SPK1 and Mcl-1 protein expression were evaluated after SPK1 interference. Cell viability was measured using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide( MTT) dye reduction assay. Cell viability was assessed by MTT after the indicated times in Dul45 cells treated with doxorubicin 1.0μg/ml and infected by adenovirus Ad-H1 or Ad-H1-SPK1. Doxorubicin-induced proliferation inhibition on Du145 was evaluate after SPK1 interference by MTT. The percentages of apoptotic cell were determined by flow cytometry analysis. Camptothecin-induced apoptosis of Du145 was evaluated after SPK1 interference.
Result: The results showed that Du145 cell expressed SPK1 signal molecule. Infected efficiency of Dul45 cells by the adenovirus is 99.92% percent(MOI=100) and meet the need of the follow-up experiment. SPK1 and Mcl-1 protein expression were significantly inhibited. Cell viability of (Ad-H1-SPK1 and doxorubicin 1μg/ml )group was lower control group (Ad-H1 + doxorubicin 1μg/ml), 48 hours for 71.2% of control and 72 hours 61.3% of control. Average cell apoptosis rate of (Ad-H1-SPK1 and camptothecin 1μM) group (58.3%) was higher than (Ad-H1 and camptothecin 1μM )group(29.1%).The difference between grops was significant (P<0.01).
Conclusion: Taken together ,these results show that SPK signaling pathway can regulate prostate cancer cell apoptosis, SPK1 interference can enhance the hormone-independent prostate cancer cells Du145 docrobicin-induced proliferation and camptothecin-induced apoptosis. These results suggest that SPK1 may be a potential new therapeutic target in hormone-independent prostate cancer cell.
前列腺癌是男性泌尿生殖系统常见的恶性肿瘤,近年来我国前列腺癌发病率逐渐上升,前列腺癌目前多采用雄激素全阻断为主的内分泌治疗,但多数病人在经过内分泌治疗后,常常转为非雄激素依赖性,成为激素难治性前列腺癌,出现复发或多发转移。传统的手术、放疗、化疗和激素疗法对激素难治性前列腺癌治疗效果不佳,目前国内外许多学者都在探求基因水平的调控方法和寻找治疗的新靶点,以期在前列腺癌的治疗上取得突破。
近年研究证明细胞膜鞘磷脂的衍生物包括神经酰胺(Cer)、鞘氨醇(Sp)、1-磷酸鞘氨醇(S1P)等多种代谢产物,在调节细胞增殖和凋亡的动态平衡中起着关键的作用。而鞘氨醇激酶(SPK)是维持细胞内上述物质平衡的重要限速酶,也是细胞增殖及存活的重要调控因子。鞘氨醇激酶信号通路与细胞的凋亡、生长、增殖密切相关,SPK1是其主要功能酶。Cer和Sp是细胞增殖的负调控因子,能够抑制细胞生长、促进细胞凋亡,S1P则刺激细胞生长、抑制细胞凋亡。SPK1磷酸化Sp生成S1P,S1P通过细胞内外作用机制调节细胞生长和凋亡。对SPK1进行调控,将影响细胞内Cer、Sp、S1P的水平,细胞内Cer、Sp、S1P的水平的高低,将影响细胞的生长、增殖和凋亡。
RNA干涉(RNAi)是近期发展起来的一种新的基因治疗和诊断技术,RNA干涉是指在多种生物细胞内,由双链RNA介导同源序列mRNA的特异性降解,从而导致基因沉默的现象。我们设想通过RNA干涉的方法,导致SPK1基因沉默,进而抑制SPK1的表达,调节神经酰胺、鞘氨醇、1-磷酸鞘氨醇在细胞内的水平,诱导非激素依赖性前列腺癌细胞的凋亡,以探讨对非激素依赖性前列腺癌细胞的基因治疗。
目的:通过检测SPK1信号分子在非激素依赖性前列腺癌细胞Du145中的表达情况,以及评价重组腺病毒Ad-H1-SPK1介导,RNA干涉Du145细胞SPK1基因,对SPK1和抗凋亡蛋白Mcl-1表达的影响;探讨重组腺病毒Ad-H1-SPK1介导,干涉SPK1对细胞凋亡的作用及可能的机制,为非激素依赖性前列腺癌细胞的基因治疗寻找新的靶点。
方法:我们选择非激素依赖性前列腺癌细胞株Du145,作为我们的实验研究对象;构建并制备了携带SPK1特异干涉序列的重组腺病毒Ad-H1-SPK1,作为介导对SPK1基因进行RNA干涉的研究工具;我们利用RT-PCR的方法,检测Du145细胞株中SPK1信号分子的表达;用腺病毒Ad-GFP作为参照,用不同滴度的腺病毒对Du145细胞进行感染,检测腺病毒对Du145的感染效率;我们用Ad-H1-SPK1感染Du-145细胞,并以不含SPK1特异干涉序列腺病毒Ad-H1作为对照,Western blot检测SPK1的表达,并用Western blot检测重要抗凋亡蛋白Mcl-1的表达,评价干涉SPK1对SPK1、Mcl-1蛋白表达的影响;用MTT的方法检测干涉SPK1,对阿霉素抑制前列腺癌细胞Du-145增殖的影响;用流式细胞仪检测细胞的凋亡情况,评价干涉SPK1对喜树碱诱导Du-145细胞凋亡的影响。
结果:我们用RT-PCR的方法,在非激素依赖性前列腺癌细胞株Du-145中检测到了SPK1信号分子的表达;我们测定腺病毒对Du-145细胞的感染效率为99.92%(MOI=100),完全可以满足后续实验的要求;用Ad-H1-SPK1感染Du-145细胞,介导对SPK1进行干涉,SPK1干涉后,SPK1、Mcl-1蛋白表达明显受到抑制,Ad-H1-SPK1+阿霉素组细胞生存率低于对照Ad-H1+阿霉素组,48小时为对照组的71.2%,72小时为对照组的61.3%:用流式细胞仪检测Du145细胞的凋亡,Ad-H1-SPK1+喜树碱组的平均细胞凋亡率58.3%,高于对照组Ad-H1+喜树碱组29.1%,经统计学处理,差异有显著性(P＜0.01)。
结论:我们的研究结果表明,SPK信号通路可以调节非激素依赖性前列腺癌细胞Du145的凋亡,靶向SPK1的RNA干扰可以抑制Du145细胞的SPK1以及重要抗凋亡蛋白Mcl-1的表达,增加阿霉素对Du145细胞增殖的抑制,增加喜树碱诱导的Du145细胞的凋亡。SPK信号通路可能为前列腺癌基因治疗提供新的靶点。
Background
Prostate cancer is one of the most common malignant tumor of the male urogenital system. In China, it' s mobidity has been rising yearly in the recent decade . Endocrine therapy of androgen blockade is the mainly treatment for prostate cancer at present. But most patients after endocrine therapy usually change into androgen-independent and become hormone refractory prostate cancer ,recurrence or metastasis .Traditional surgery, radiotherapy, chemotherapy and endocrine therapy are ineffective for hormone refractory prostate cancer. Many scholars explore at the level of gene regulation and control to the treatment of prostate cancer,and look for a new target for treatment to make a breakthrough . In recent years, studies have proved that membrane sphingomyelin derivatives include ceramide (Cer), sphingosine (Sp), sphingosine-1- phosphate (S1P) and other metabolites .They plays a key role in the dynamic equilibrium regulation of cell proliferation and apoptosis . The sphingosine kinase (SPK) is important rate-limiting enzyme to maintain the intracellular balance of these substances. It was important regulatory factors of cell proliferation and survival. The cell levels of these sphingolipid metabolites are regulated by sphingosine kinase (SPK) which phosphorylates Sp to form S1P and regulates its cellular levels. Sphingosine kinase signaling pathway are closely related with cell apoptosis, growth and proliferation.
RNA interference (RNAi) is recently developed a new gene therapy and diagnostic technology. RNA interference happen in a variety of biological cells .It is special phenomenon that double-stranded RNA mediated homologous sequence specific mRNA degradation and led to gene silencing. We envisage that RNA interference cause SPK1 gene silencing, thereby inhibiting the expression of SPK1, regulating ceramide, sphingosine-l-phosphate,sphingosine intracellular level, Induced apoptosis of hormone-independent prostate cancer cell. It was explored for hormone-independent prostate cancer gene therapy.
OBJICTIVER: SPK1 signal molecule expression were examined in the hormone-independent prostate cancer cells line Du145. SPK1 and Myeloid cell leukemia-1 (Mcl-1) expression were examined after recombinant adenovirus Ad-H1-SPK1 mediated SPK1 interference on Dul45 cell .It was discussed that SPK1 interference play role on Du145 cell apoptosis and possible mechanism. We want to look for a new target for hormone-independent prostate cancer gene therapy.
Method: The hormone-independent prostate cancer Du145 cell was selected as experimental subject. Recombinant adenovirus Ad-H1-SPK1 which carry SPK1 specific interference sequence was built and prepared, as an research tool to mediat RNA interference for SPK1 gene. RT-PCR method was used to measure SPK1 signal molecule expression on Du145. Infected efficiency of Du145 was tasted with adenovirus Ad-GFP as a reference. Adenovirus Ad-H1 which not to carry SPK1 specific interference sequence was as control. SPK1 and Mcl-1 expression was measured by Western blotting. Influence of SPK1 and Mcl-1 protein expression were evaluated after SPK1 interference. Cell viability was measured using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide( MTT) dye reduction assay. Cell viability was assessed by MTT after the indicated times in Dul45 cells treated with doxorubicin 1.0μg/ml and infected by adenovirus Ad-H1 or Ad-H1-SPK1. Doxorubicin-induced proliferation inhibition on Du145 was evaluate after SPK1 interference by MTT. The percentages of apoptotic cell were determined by flow cytometry analysis. Camptothecin-induced apoptosis of Du145 was evaluated after SPK1 interference.
Result: The results showed that Du145 cell expressed SPK1 signal molecule. Infected efficiency of Dul45 cells by the adenovirus is 99.92% percent(MOI=100) and meet the need of the follow-up experiment. SPK1 and Mcl-1 protein expression were significantly inhibited. Cell viability of (Ad-H1-SPK1 and doxorubicin 1μg/ml )group was lower control group (Ad-H1 + doxorubicin 1μg/ml), 48 hours for 71.2% of control and 72 hours 61.3% of control. Average cell apoptosis rate of (Ad-H1-SPK1 and camptothecin 1μM) group (58.3%) was higher than (Ad-H1 and camptothecin 1μM )group(29.1%).The difference between grops was significant (P<0.01).
Conclusion: Taken together ,these results show that SPK signaling pathway can regulate prostate cancer cell apoptosis, SPK1 interference can enhance the hormone-independent prostate cancer cells Du145 docrobicin-induced proliferation and camptothecin-induced apoptosis. These results suggest that SPK1 may be a potential new therapeutic target in hormone-independent prostate cancer cell.
引文
[1]Parkin DM,Bray F,Ferlay J,et al.Global cancer statistics,2002.CA Cancer J Clin,2005,55:742108.
[2]Ferlay J,Bray F,Pisani P,et al.GLOBOCAN 2002 Cancer Incidence,Mortality and PrevalenceWorldwide[cited 2005211221].Available from:URL:http://www2dep.iarc.fr/globocan/GLOBOCAN 2002_Sep tember_2005.ZIP
[3]张薇,项永兵,刘振伟,等.上海市区老年人泌尿系统常见恶性肿瘤发病趋势分析(1973-1999年).癌症,2004,23:555-558.
[4]Leung R,Paul A.RNA interference:from gene silencing to gene- specific therapeutics.Pharmacology & Therapeutics,2005,107:222 - 239.
[5]Bass BL Double - stranded RNA as a temp late for gene silencing.Cell,2000,101:235 - 238.
[6]Sijen T,Flessnor J,Simmer F,et al.On the role of RNA amp lification in dsRNA - triggered gene silencing..Cell,2001,107(4):465 - 467.
[7]Eastham JA,Grafton W,Martin CM.et al.Suppression of primary tumor growth and the progression to metastasis with p53 adenovirus in human prostate cancer.J Urol 2000;164(3 Pt 1):814-819.
[8]Harrington KJ,Spitzweg C,Bateman AR,et al.Gene therapy for prostate cancer:current status and future prospects.J Urol,2001;166(4):1220-1233
[9]Bernard D,Pourtier - Manzanedo A,Gil J,et al.Myc confers androgen -independent prostate cancer cell growth.J Clin Invest,2003,112(11):1724-1731.
[10]Lee SO,Lou W,Qureshi KM,et al.RNA interference targeting Stat3 inhibits growth and induces apoptosis of human prostate cancer cells.Prostate,2004,60(4):303-309.
[11]Grzmil M,Thelen P,Hemmerlein B,et al.Bax inhibitor - 1 is overexpressed in prostate cancer and its specific down - regulation by RNA interference leads to cell death in human prostate carcinoma cells.Am J Patho1,2003,163(2):543 - 552.
[12]Tan C,Cruet - Hennequart S,Troussard A,et al.Regulation of tumor angiogenesis by integrin linked kinase(ILK).Cancer Cell,2004,5(1):79-90.
[13] Mincheff M,Altankova I , Zoubak S et al . In vivo transfection and/ or coss-riming of dendritic cells following DNA and adenoviral immunizations for immunotheraphy of cancer changes in peripheral mononuclearsubsets and intracellular IL-4 and IFN-gamma lymphokine profile .Crit Rev Oncol Hematol ,2001,39 (1-2) : 125-132.
[14] Hamilton AJ , Baulcombe DC. A species of small antisense RNA in posttranscriptional gene silencing in plants . Science, 1999 ,286 (5441): 950-952.
[15] Hammond SM , Boettcher S , Caudy A A ,et al. Argonaute2 , a link between genetic and biochemical analyses of RNAi . Science , 2001 , 293 (5532) : 1146 - 1150.
[16] Elbashir SM , Lendeckel W, Tuschel T. RNA interference is mediated by 21- and 22-nucleotide RNAs[J ]. Genes Dev, 2001,15(2): 188-200.
[17] Phillip AS. RNA interference-2001. Genes Dev, 2001,15(5): 485-489.
[18] Hait NC, Oskeritzian CA,Paugh SW,et,al. Sphingosine kinases, sphingosine 1-phosphate, apoptosis and diseases. Biochim Biophys Acta. 2006,1758(12):2016-26.
[19] Maceyka M, Payne SG, Milstien S,et, al.Sphingosine kinase, sphingosine-l-phosphate,and apoptosis. Biochim Biophys Acta. 2002 ,1585 (2-3): 193-201.
[20] Cuvillier O. Sphingosine in apoptosis signaling. Biochim Biophys Acta. 2002,1585(2-3): 153-162.
[21] Alemany R, van Koppen CJ, Danneberg K,et,al. Regulation and functional roles of sphingosine kinases. Naunyn Schmiedebergs Arch Pharmacol. 2007,374(5-6): 413-28.
[22] Liu H, Chakravarty D, Maceyka M,et,al. Sphingosine kinases: a novel family of lipid kinases. Prog Nucleic Acid Res Mol Biol. 2002;71:493-511.
[23] Kohama T, Olivera A, Edsall L,et,al. Molecular cloning and functional characterization of murine sphingosine kinase.J Biol Chem. 1998 , 273(37): 23722-23728.
[24] Gulbins E. Regulation of death receptor signaling and apoptosis by ceramide J . Pharmacol Res, 2003,47(5):393 - 399.
[25] Victor E. Nava, Olivier Cuvillier, Lisa C. Edsall,et,al Sphingosine Enhances Apoptosis of Radiation-resistant Prostate Cancer Cells ,Cancer Res,2000, 60: 4468-4474.
[26] Dimitri Pchejetski,Muriel Golzio, Elisabeth Bonhoure,et,al.Sphingosine Kinase-1 as a Chemotherapy Sensor in Prostate Adenocarcinoma Cell and Mouse Models Cancer Res ,2005; 65: (24): 11667-11675.
[27] Kohama T, Olivera A, EdsallL, et al. Molecular cloning and functional characterization of murine sphingosine kinase .J Biol Chem, 1998, 273(37): 23722-23728.
[28] Jorgenson R. Altered gene exp ression in p lants due to trans interactions between homologous genes. Trends Biotechnol, 1990,8(12): 340 - 344.
[29] Cogoni C,Romano N ,Macino G.Suppression of gene expression homologos transgenes [J]Antonie Van Leeuwenhoek,1994,65(3):205-209.
[30] Guo S, Kemphues K J. Par21, a gene required for establishing polarity in C. elegans embryos, encodes a putative Ser/Thr kinase that is asymmetrically distributed . Cell,1995,81(4):611-620.
[31] Fire A, Xu S, MontgomeryM K, et al. Potent and specific genetic interference by double-stranded RNA in caenorhabditis elegans[ J ]. Nature, 1998, 391 (6669): 806 -11.
[32] William M, Winston, C M, Craig P H. Systemic RNAi in C.elegans Requires the Putative Transmembrane Protein SID-1 . Science, 2002,295(29):2456-2459.
[33] Lipardi C,Wei Q, Paterson BM.RNAi as random degradative PCR: siRNA primers convert mRNA into dsRNAs that are degraded to generate new siRNAs. Cell, 2001,107( 3): 297- 307.
[34] Garzon R, Pichiorri F, Palumbo T, et al. Micro RNA fingerprints during human megakaryocytopoiesis. PANS , 2006,103 (13): 5078- 5083.
[35] Horvitz HR, Sulston JE. Isolation and genetic characterization of cell-lineage mutants of the nematode caenorhnbditis elegans[ J ]. Genetics, 1980,96 (2): 435 - 454.
[36] Elbashir SM, LendeckelW, Tuschl T. RNA interference is mediated by 21 and 22 nueleotide RNAs . Genes Development, 2001, 15(2): 188 - 200.
[36] Hutvagner G, McLachlan J, PasquinelliAE, et al. A cellular functionof for the RNA-interference enzyme Dicer in the maturation of the let27small temporal RNA. Science, 2001,293 (5531): 834 - 838.
[37] Wu LG, Fan JH, Belasco JG. MicroRNAs direct rapid deadenylation of mRNA. PNAS , 2006,103 (11): 4034 - 4039.
[38] Ruts S, Scheffold A. Towards in vivo application of RNA interference new toy, old problems . Arthritis Res Ther,2004,6: 78 - 85.
[39] Elbashir SM, Harborth J, Lendeckel W, et al. Duplexes of 21-nucleotide RNAs mediate RNA interference in cultured mammalian cells . Nature,2001, 411(6836): 494-498.
[40] Bass BL.RNA interference.The short answer .Nature, 2001,411 (6836): 428- 429.
[41] Brake O, Berkhout B. Lentiviral vectors that carry anti-H IV shRNAs: problems and solutions. J GeneMed, 2007,9:743 - 750.
[42] Mizuguchi H, FunakoshiN, Hosono T, et al. Rapid construction of small interfering RNA-expressing adenoviral vectors on the basis of direct cloning of short hairp in RNA-coding DNAs. Hum Gene Ther, 2007,18: 74 - 80.
[43] Storvold GL, Gjernes E, Askautrud HA, et al. A retroviral vector for siRNA exp ression in mammalian cells . MolBiotechnol, 2007, 35: 275 - 282.
[44] Pchejetski D, Golzio M, Bonhoure E, et al.Sphingosine kinase-1 as a chemotherapy sensor in prostate adenocarcinoma cell and mouse models. Cancer Res. 2005 ,65(24): 11667-11675.
[45] Nava VE, Cuvillier O, Edsall LC, et al. Sphingosine enhances apoptosis of radiation-resistant prostate cancer cells. Cancer Res 2000,60,4468-4474.
[46] Bourbon NA ,Yun J ,Kester M. Ceramide directly activates protein kinase C zeta to regulate a stress-activated protein kinase signaling complex J Biol Chem ,2000,275 (45) :35617-356231
[47] Ruvolo PP. Intracellular signal transduction pathways activated by ceramide and its metabolites . Pharmacol Res ,2003 ,47 (5):383-392.
[48] Jarvis WD, Fornari FA J r ,Auer KL, et al.Coordinate regulation of stress and mintgen activated protein kinase in the apoptotic actions of ceramide and sphingosine. Mol Pharmacol ,1997 ,52 (6) :935947.
[49] Willaime S ,Vanhoutte P ,Caboche J , et al. Ceramide-induced apoptosis in cortical neurons is mediated by an increase in p38 phosphorylation and not by the decrease in ERK phosphorylation .Eur J Neurosci .2001,13 (11) :2037-2046
[50] Edsall LC, Spiegel S. Enzymatic measurement of sphingosine 1-phosphate. Anal Biochem 1999,272:80-6.
[51] Hla T. Signaling and biological actions of sphingosine 1-phosphate. Pharmacol Res. 2003; 47(5):401-407.
[52] Spiegel S, Milstien S, Functions of a new family of sphingosine -1-phosphate receptors. Biochim. Biophys. Acta .2000,1484:107-116
[53] Spiegel S, Milstien S. Sphingosine-1-phosphate: an enigmatic signaling lipid.Nat Rev Mol Cell Biol. 2003,4:397-407.
[54] Spiegel S, Milstien S, Sphingosine 1-phosphate, a key cell signaling moleculeJ Biol Chem 2002,277 :25851-25854.
[55] Cuvillier O, Pirianov G, Kleuser B, et al. Suppression of ceramide-mediated programmed cell death by sphingosine-1-phosphate. Nature, 1996, 381(6585): 800-803.
[57] Hideshima T, Nakamura N, Chauhan D, Anderson KC. Biologic sequelae of interleukin-6 induced PI3-K/Akt signaling in multiple myeloma. Oncogene .2001, 20:5991-6000.
[58] Podar K, Mostoslavsky G, Sattler M, et al. Critical role for hematopoietic cell kinase (Hck)-mediated phosphorylation of Gab1 and Gab2 docking proteins in interleukin 6-induced proliferation and survival of multiple myeloma cells. J Biol.Chem .2004 279:21658-65.
[59] Le Scolan E, Pchejetski D, Banno Y, et al. Overexpression of sphingosine kinasel is an oncogenic event in erythroleukemic progression. Blood. 2005 ,106(5): 1808-1816.
[60] Xia P, Gamble JR, Wang L, et al. An oncogenic role of sphingosine kinases . Curr Biol, 2000,10(23): 1527-1530.
[61] Olivera A, Spiegel S. Sphingosine-1-phosphate as second messenger in cell proliferation induced by PDGF and FCS mitogens. Nature (1993) 365:557-60.
[62] Pitson SM, Moretti PA, Zebol JR, et al. The nucleotide-binding site of human sphingosine kinase 1. J Biol Chem (2002) 277:49545-53.
[63] Wu W, Mosteller RD, Broek D. Sphingosine kinase protects lipopolysaccharide- activated macrophages from apoptosis. Mol Cell Biol (2004) 24: 7359-69.
[64] Bonhoure E, Pchejetski D, Aouali N, et al. Overcoming MDR-associated chemoresistance in HL-60 acute myeloid leukemia cells by targeting shingosine kinase-1.Leukemia .2005;[Epub ahead of print]
[65] Baltzer AW , Lattermann C , Whalen JD , et al . Genetic enhancenent of fracture repair : healing of an experimental sepmental defect by adenoviral transfer of the BMP-2 gene J . Gene Ther, 2000,7(9): 7342739.
[66] Baltzer AM , Lattermann C , Whalen JD , et al . Potential role of direct adenoviral gene transfer in enhancing fracture repair J . Clin Orthop , 2000 , ( 379 Suppl):S120-S125.
[67] Alden TD , Pittman DD , Hankins GR , et al. In vivo endochron dral bone formation using a bone morphogenetic protein 2 adenoviral vector[J ]. Hum Gene Ther, 1999,10(13): 224522253.
[68] Bergelson JM, Cunningham JA, Droguett G, et al. Isolation of common receptor for Coxsackie B viruses and adenoviruses 2 and 5 . Science, 1997, 275 (5304): 1320 -1323.
[69] Wickham TJ, Mathias P, Cheresh DA, et al. Integrins alpha beta 3 and alphav beta 5 promote adenovirus internalization not virus attachment. Cell, 1993, 73 (2) :309 -319.
[70] Bauerschmitz GJ, Barker SD, Hemminki A. Adenoviral gene therapy for cancer: from vectors to targeted and replication competent agents . Int J Oncol, 2002, 21 (6): 1161-1174.
[71] Wickham TJ, SegalDM, Roelvink PW, et al. Targeted adenovirus gene transfer to endothelial and smooth muscle cells by using bispecific antibodiesJ . J Virol, 1996,70 (10): 6831-6838.
[72] Watkins SJ, Mesyanzhinov VV, Kurochkina LP, et al. The 'adenobody' approach to viral targeting: specific and enhanced adenoviral gene delivery . Gene Ther, 1997,4(10): 1004-1012.
[73] Dmitriev I, Kashentseva E, Rogers BE, et al. Ectodomain of coxsackie virus and adenovirus recep tor genetically fused to epidermal growth factor mediates adenovirus targeting to epidermal growth factor receptor positive cells. J Virol, 2000, 74 (15) :6875 - 6884.
[74] HemminkiA, Dmitriev I, Liu B, et al. Targeting oncolytic adenoviral agents to the epidermal growth factor pathwaywith a secretory fusion molecule. Cancer Res, 2001,61 (17): 6377-6381.
[75] Ogretmen B, Hannun YA. Biologically active sphingolipids in cancer pathogenesis and treatment. Nat Rev Cancer .2004,4:604-616.
[76] Nava VE, Hobson JP, Murthy S,et al.Sphingosine kinase type 1 promotes estrogen-dependent tumorigenesis of breast cancer MCF-7 cells. Exp Cell Res. 2002,281:115-127.
[77] French KJ, Schrecengost RS, Lee BD, et al. Discovery and evaluation of inhibitors of human sphingosine kinase. Cancer Res 2003,63:5962-5969.
[78] Nava VE, Cuvillier O, Edsall LC, et al. Sphingosine enhances apoptosis of radiation-resistant prostate cancer cells. Cancer Res 2000,60,4468-4474.
[79] Liu H, Sugiura M, Nava VE, et al. Molecular cloning and functional characterization of a novel mammalian sphingosine kinase type 2 isoform [J]. Biol Chem, 2000, 275(26): 19513-20
[80] Spiegel s, Kolesnick R.Sphingosine 1-phosphate as a therapeutic agent. Leukemia. 2002 Sep: 16(9): 1596-602.
[81] Sadahira Y, Ruan F, Hakomori S, et al. Sphingosine 1-Phosphate, a Specific Endogenous Signaling Molecule Controlling Cell Motility and Tumor Cell Invasiveness. Proc. Natl. Acad. Sci. U.S.A. 1992, 89:9686-9690.
[82] Lee MJ, Van Brocklyn JR, Thangada S, et al. Sphingosine-1-Phosphate as a Ligand for the G Protein-Coupled Receptor EDG-1. Science, 1998, 279:1552-1555.
[83] Edsall LC, Cuvillier O, Twitty S, et al. .Sphingosine kinase expression regulates apoptosis and caspase activation in PC12 cells.J Neurochem.2001,76:1573-1584.
[84]Chang HC,Hsu C,Hsu HK,et al.Functional role of caspases in sphingosine-induced apoptosis in human hepatoma cells.IUBMB Life,2003,55(7):403-7.
[85]Craig R W.Mcl-1 provides a window on the role of the BCL-2 family in cell proliferation,differentiation and tunorigenesis.Leukemia.2002,16(5):444 - 454.
[86]Nijhawan D,Fang M,Traer E,et al.Elimination of Mcl-1 is required for t he initiation of apoptosis following ultraviolet irradiation.Genes Dev,2003,17(12):1475-1486.
[87]Dererme S,Monia B,Dean N M,et al.Antisense strategy shows that Mcl-1rather than Bcl-2 or Bcl2x(L) is an essential survival protein of human myeloma cells.Blood.2002,100(1):194 - 199.
[88]Zhang B,Gojo I,Fenton R G.Myeloid cell factor-1 is a critical survival factor for multiple myeloma.Blood,2002,99(6):1885 - 1893.
[89]Francesco Fabbril,Giovanni Brigliadoril,Silvia Carlonil,et al.Zoledronic acid increases docetaxel cytotoxicity through pMEK and Mcl-1 inhibition in a hormone-sensitive prostate carcinoma cell line.J Tran Med 2008,6(43):1-10.
[90]Cavarretta IT,Neuwirt H,Untergasser G,et al.The antiapoptotic effect of IL-6autocrine loop in a cellular model of advanced prostate cancer is mediated by Mcl-1.Oncogene.2007,26:2822-2832.
[91]Bernhard Gillissen,Frank Essmann,Philipp G,et al.Mcl-1 determines the Bax dependency of Nbk/Bik-induced apoptosis.J.Cell Biol.2007,179(4):701-715.
[92]Krajewski S,Bodrug S,Krajewski M,et al.Immunohistochemical analysis of Mcl-1 protein in human tissues.AmJ Pathol.1995,146(6):1309-1319.
[93]Craig RW.Mcl-1 provides a window on the role of the BCL2 family in cell proliferation differentiation and tumorigenesis.Leukemia(2002) 16:444-454.
[94]Le Gouill S,Podar K,Amiot M,et al.VEGF induces Mcl-1 up-regulation and protects multiple myeloma cells against apoptosis.Blood(2004) 104:2886-9
[95]Puthier D,Bataille R,Amiot M.IL-6 up-regulates mcl-1 in human myeloma cells through JAK / STAT rather than ras / MAP kinase pathway.Eur J Immunol.1999,29(12):3945-50.
[96]P.K.Epling-Burnette,Jin Hong Liu,Robyn Catlett-Falcone,et al.Inhibition of STAT3 signaling leads to apoptosis of leukemic large granular lymphocytes and decreased Mcl-1 expression.J.Clin.Invest.2001.107:351-362.
[97]Kuo ML,Chuang SE,Lin MT,et al.The involvement of PI 3-K/Akt-dependent up-regulation of Mcl-1 in the prevention of apoptosis of Hep3B cells by interleukin-6.Oncogene.2001;20(6):677-85.
[98]Jourdan M,Veyrune JL,Vos JD,et al.A major role for Mcl-1 antiapoptotic protein in the IL-6-induced survival of human myeloma cells.Oncogene.2003;22(19):2950-9.
[99]Sano J,Oguma K,Kano R,Hasegawa A.Molecular cloning of canine Mcl-1gene and its expression in tumor cell lines.J Vet Med Sci.2004;66(6):709-12.
[100]Johnston JB,Paul JT,Neufeld NJ,Haney N,Kropp DM,Hu X,Cheang M,Gibson SB.Role of myeloid cell factor-1(Mcl-1) in chronic lymphocytic leukemia.Leuk Lymphoma.2004;45(10):2017-27.
[101]Opferman JT,Letai A,Beard C,et al.Development and maintenance of B and T lymphocytes requires antiapoptotic MCL-1.Nature.2003;426(6967):671-6.
[102]Le Gouill S,Podar K,Amiot M,Hideshima T,Chauhan D,VEGF induces Mcl-lup-regulation and protects multiple myeloma cells against apoptosis.Blood.2004;104(9):2886-92..
[103]Derenne S,Monia B,Dean NM,et al.Antisense strategy shows that Mcl-1rather than Bcl-2 or Bcl-x(L) is an essential survival protein of human myeloma cells.Blood.2002;100:194-9.
[104]Leo CP,Hsu SY,Chun SY,Bae HW,Hsueh AJ.Characterization of the antiapoptotic Bcl-2 family member myeloid cell leukemia-1(Mcl-1) and the stimulation of its message by gonadotropins in the rat ovary.Endocrinology.1999;140:5469-77.
[105]Maryla K,Stanislaw K,Jonathan,IE,et al.Immunohistochemical Analysis of bcl-2,bax,bcl-X,and mcl-1 Expression in Prostate Cancers.Am J Pathol 1996,148(5):1567-1576.
[106] Li QF, Wu CT, Duan H.F, et,al. Activation of sphingosine kinase mediates suppressive effect of interleukin-6 on human multiple myeloma cell apoptosis. Br J Haematol .2007; 138 632-39.
[107] El-Zawahry A, McKillop J, Voelkel-Johnson C.Doxorubicin increases the effectiveness of Apo2L/TRADL for tumor growth inhibition of prostate cancer xenografts. BMC Cancer. 2005 ,7;5:2
[108] Kelly MM, Hoel BD, Voelkel-Johnson C Doxorubicin pretreatment sensitizes prostate cancer cell lines to TRAIL induced apoptosis which correlates with the loss of c-FLIP expression. Cancer Biol Ther. 2002; 1(5):528-9.
[109] Brusselmans K, De Schrijver E, Verhoeven G, et al . RNA interference-mediated silencing of the acetyl-CoA-carboxylase-alpha gene induces growth inhibition and apoptosis of prostate cancer cells. Cancer Res. 2005 , 65(15):6719-6725.
[110] Liao X, Tang S, Thrasher JB,et al. Small-interfering RNA-induced androgen receptor silencing leads to apoptotic cell death in prostate cancer. Mol Cancer Ther. 2005,4(4):505-515.
[111] Grzmil M, Thelen P, Hemmerlein B, et al.Bax inhibitor-1 is overexpressed in prostate cancer and its specific down-regulation by RNA interference leads to cell death in human prostate carcinoma cells. Am J Pathol. 2003,163(2):543-552
[112] Grzmil M, Thelen P, Hemmerlein B, et al.Bax inhibitor-1 is overexpressed in prostate cancer and its specific down-regulation by RNA interference leads to cell death in human prostate carcinoma cells. Am J Pathol. 2003,163(2):543-552
[113] De Schrijver E, Brusselmans K, Heyns W, et al.RNA interference-mediated silencing of the fatty acid synthase gene attenuates growth and induces morphological changes and apoptosis of LNCaP prostate cancer cells.Cancer Res. 2003 ,63 (13):3799-3804.
[114] Song J, Pang S, Lu Y, et al. Gene silencing in androgen-responsive prostate cancer cells from the tissue-specific prostate-specific antigen promoter. Cancer Res. 2004,64(21):7661-7663
[115] Brusselmans K, De Schrijver E, Verhoeven G, et al.RNA interference- mediated silencing of the acetyl-CoA-carboxylase-alpha gene induces growth inhibition and apoptosis of prostate cancer cells.Cancer Res.2005,65(15):6719-6725.
[116]Assikis VJ,Simons JW.Novel therapeutic strategies for androgen-independent prostate cancer:an update.Semin Oncol.2004,31:26-32.
[117]Cuvillier O,Sphingosine kinase-1 a potential therapeutic target in cancer.Anticancer Drugs 2007,18:105-110.
[118]Sabbadini R.A.Targeting sphingosine-1-phosphate for cancer therapy.Br J Cancer.2006;95:1131-1135.
[119]Ryo A,Uemura H,Ishiguro H,et al.Stable suppression of tumorigenicity by Pin1-targeted RNA interference in prostate cancer.Clin Cancer Res.2005,11(20):7523-7531
[120]Han B,Xie H,Chen Q,et al.Sensitizing hormone-refractory prostate cancer cells to drug treatment by targeting 14-3-3sigma.Mol Cancer Ther.2006,5(4):903-912.
[1] Jorgenson R. Altered gene exp ression in p lants due to trans interactions between homologous genes. Trends Biotechnol, 1990,8(12): 340 - 344.
[2] Cogoni C,Romano N ,Macino G.Suppression of gene expression homologos transgenes [J]Antonie Van Leeuwenhoek,1994,65(3):205-209.
[3] Guo S, Kemphues K J. Par21, a gene required for establishing polarity in C. elegans embryos, encodes a putative Ser/Thr kinase that is asymmetrically distributed . Cell,1995,81(4):611-620.
[4] Fire A, Xu S, MontgomeryM K, et al. Potent and specific genetic interference by double-stranded RNA in caenorhabditis elegans[ J ]. Nature, 1998, 391 (6669) : 806 -11.
[5] William M, Winston, C M, Craig P H. Systemic RNAi in C.elegans Requires the Putative Transmembrane Protein SID-1. Science, 2002,295(29):2456-2459.
[6] Garzon R, Pichiorri F, Palumbo T, et al. Micro RNA fingerprints during human megakaryocytopoiesis. PANS , 2006,103 (13): 5078- 5083.
[7] Horvitz HR, Sulston JE. Isolation and genetic characterization of cell-lineage mutants of the nematode caenorhnbditis elegans[ J ]. Genetics, 1980,96 (2): 435 - 454.
[8] Elbashir SM, LendeckelW, Tuschl T. RNA interference is mediated by 21 and 22 nueleotide RNAs . Genes Development, 2001,15(2): 188 - 200.
[9] Hutvagner G, McLachlan J, PasquinelliAE, et al. A cellular functionof for the RNA-interference enzyme Dicer in the maturation of the let27 small temporal RNA. Science, 2001,293 (5531): 834 - 838.
[10] Wu LG, Fan JH, Belasco JG. MicroRNAs direct rapid deadenylation of mRNA. PNAS , 2006,103 (11): 4034 - 4039.
[11] Buratowski S, Moazed D. Gene regulation: Expression and silencing coupled. Nature, 2005,435 (7046): 1174 -1175.
[12] Elbashir SM, Harborth J, Lendeckel W, et al. Duplexes of 21-nueleotide RNAs mediate RNA interference in cultured mammalian cells . Nature,2001, 411(6836): 494-498.
[13]Bass BL.RNA interference.The short answer.Nature,2001,411(6836):428-429.
[14]Sioud M.Therapeutic siRNAs[J].Trends Pharmacol Sci,2004,25(1):22-28.
[15]Elbashir SM,Harborth J,Lendeckel W,et al.Duplexes of 21-nu-cleotide RNAs mediate RNA interference in cultured mammalian cells[J].Nature,2001,411:428 - 429.
[16]Bernard D,Pourtier - Manzanedo A,Gil J,et al.Myc confers androgen -independent prostate cancer cell growth.J Clin Invest,2003,112(11):1724-1731.
[17]Lee SO,Lou W,Qureshi KM,et al.RNA interference targeting Stat3 inhibits growth and induces apoptosis of human prostate cancer cells.Prostate,2004,60(4):303-309.
[18]Grzmil M,Thelen P,Hemmerlein B,et al.Bax inhibitor - 1 is overexpressed in prostate cancer and its specific down - regulation by RNA interference leads to cell death in human prostate carcinoma cells.Am J Patho1,2003,163(2):543 - 552.
[19]Brummelkamp TR,Bemards R.New tools for functional animal cancer genetics[J].Nat Rev Cancer,2003,3:781 - 791.
[20]Hannon GJ,Rossi J.Unlocking the potential of the human genome with RNA interference[J].Nature,2004,431:371 - 378.
[1] Leung R, Paul A. RNA interference: from gene silencing to gene- specific therapeutics. Pharmacology & Therapeutics, 2005,107:222 - 239.
[2]Eastham JA, Grafton W, Martin CM. et al. Suppression of primary tumor growth and the progression to metastasis with p53 adenovirus in human prostate cancer. J Urol 2000;164(3 Pt 1): 814-819.
[3] Harrington KJ ,Spitzweg C ,Bateman AR ,et al . Gene therapy for prostate cancer: current status and future prospects J Urol ,2001; 166(4) :1220- 1233
[4] Bernard D ,Pourtier - Manzanedo A ,Gil J ,et al .Myc confers androgen -independent prostate cancer cell growth. J Clin Invest ,2003 ,112(11):1724-1731.
[5] Lee SO ,Lou W,Qureshi KM,et al . RNA interference targeting Stat3 inhibits growth and induces apoptosis of human prostate cancer cells.Prostate ,2004 , 60(4):303-309.
[6]Grzmil M.Thelen P ,Hemmerlein B ,et al. Bax inhibitor - 1 is overexpressed in prostate cancer and its specific down - regulation by RNA interference leads to cell death in human prostate carcinoma cells. Am J Pathol ,2003 ,163 (2) :543 - 552.
[7] Tan C, Cruet - Hennequart S, Troussard A, et al. Regulation of tumor angiogenesis by integrin linked kinase(ILK). Cancer Cell, 2004,5(1):79-90.
[8]Mincheff M,Altankova I , Zoubak S et al . In vivo transfection and/ or coss-riming of dendritic cells following DNA and adenoviral immunizations for immunotheraphy of cancer changes in peripheral mononuclearsubsets and intracellular IL-4 and IFN-gamma lymphokine profile [J ] .Crit Rev Oncol Hematol ,2001,39 (1-2):125-132.
[9]Ohanian J , Ohanian V. Sphingolipids in mammalian cell signalling.[J].Cell Mol Life Sci, 2001,58 (14) : 2053- 2068.
[10] Hait NC, Oskeritzian CA,Paugh SW,et,al. Sphingosine kinases, sphingosine 1-phosphate, apoptosis and diseases. Biochim Biophys Acta. 2006,1758(12):2016-26.
[11]Maceyka M, Payne SG, Milstien S,et, al.Sphingosine kinase,sphingosine- 1-phosphate,and apoptosis. Biochim Biophys Acta. 2002,1585(2-3): 193-201.
[12]Cuvillier O. Sphingosine in apoptosis signaling._Biochim Biophys Acta. 2002 ,1585(2-3): 153-162.
[13]Alemany R, van Koppen CJ, Danneberg K,et,al. Regulation and functional roles of sphingosine kinases. Naunyn Schmiedebergs Arch Pharmacol. 2007,374 (5-6):413-28.
[14] Liu H, Chakravarty D, Maceyka M,et,al. Sphingosine kinases: a novel family of lipid kinases. Prog Nucleic Acid Res Mol Biol. 2002;71:493-511.
[15]Kohama T, Olivera A, Edsall L,et,al. Molecular cloning and functional characterization of murine sphingosine kinase.[J]J Biol Chem. 1998 , 273(37): 23722-23728.
[16]Gulbins E. Regulation of death receptor signaling and apoptosis by ceramide[ J ]. Pharmacol Res, 2003,47(5):393 - 399.
[17] Edsall LC, Cuvillier O, Twitty S, et al. Sphingosine kinase expression regulates apoptosis and caspase activation in PC 12 cells [J]. Neurochem, 2001, 76(5): 1573-84.
[18] Chang HC, Hsu C, Hsu HK, et al. Functional role of caspases in sphingosine-induced apoptosis in human hepatoma cells [J]. IUBMB Life, 2003, 55(7): 403-7.
[19]Xia P, Gamble JR, WangL, et al. An oncogenic role of sphingosine kinase[ J ]. Curr Biol, 2000,10 (23): 1527 -1530.
[20] Olivera A, Kohama T, Edsall L, et al. Sphingosine kinase expression increases intracellular sphingosine-1-phosphate and promotes cell growth and survival [ J ]. J Cell Biol, 1999,147 (3 ) :545 - 558.
[21]Victor E. Nava, Olivier Cuvillier, Lisa C. Edsall,et,al Sphingosine Enhances Apoptosis of Radiation-resistant Prostate Cancer Cells ,Cancer Res,2000,60:4468-4474.
[22]Dimitri Pchejetski,Muriel Golzio, Elisabeth Bonhoure,et,al Sphingosine Kinase-1 as a Chemotherapy Sensor in Prostate Adenocarcinoma Cell and Mouse Models Cancer Res ,2005; 65: (24):11667-11675.
[2]Ferlay J,Bray F,Pisani P,et al.GLOBOCAN 2002 Cancer Incidence,Mortality and PrevalenceWorldwide[cited 2005211221].Available from:URL:http://www2dep.iarc.fr/globocan/GLOBOCAN 2002_Sep tember_2005.ZIP
[3]张薇,项永兵,刘振伟,等.上海市区老年人泌尿系统常见恶性肿瘤发病趋势分析(1973-1999年).癌症,2004,23:555-558.
[4]Leung R,Paul A.RNA interference:from gene silencing to gene- specific therapeutics.Pharmacology & Therapeutics,2005,107:222 - 239.
[5]Bass BL Double - stranded RNA as a temp late for gene silencing.Cell,2000,101:235 - 238.
[6]Sijen T,Flessnor J,Simmer F,et al.On the role of RNA amp lification in dsRNA - triggered gene silencing..Cell,2001,107(4):465 - 467.
[7]Eastham JA,Grafton W,Martin CM.et al.Suppression of primary tumor growth and the progression to metastasis with p53 adenovirus in human prostate cancer.J Urol 2000;164(3 Pt 1):814-819.
[8]Harrington KJ,Spitzweg C,Bateman AR,et al.Gene therapy for prostate cancer:current status and future prospects.J Urol,2001;166(4):1220-1233
[9]Bernard D,Pourtier - Manzanedo A,Gil J,et al.Myc confers androgen -independent prostate cancer cell growth.J Clin Invest,2003,112(11):1724-1731.
[10]Lee SO,Lou W,Qureshi KM,et al.RNA interference targeting Stat3 inhibits growth and induces apoptosis of human prostate cancer cells.Prostate,2004,60(4):303-309.
[11]Grzmil M,Thelen P,Hemmerlein B,et al.Bax inhibitor - 1 is overexpressed in prostate cancer and its specific down - regulation by RNA interference leads to cell death in human prostate carcinoma cells.Am J Patho1,2003,163(2):543 - 552.
[12]Tan C,Cruet - Hennequart S,Troussard A,et al.Regulation of tumor angiogenesis by integrin linked kinase(ILK).Cancer Cell,2004,5(1):79-90.
[13] Mincheff M,Altankova I , Zoubak S et al . In vivo transfection and/ or coss-riming of dendritic cells following DNA and adenoviral immunizations for immunotheraphy of cancer changes in peripheral mononuclearsubsets and intracellular IL-4 and IFN-gamma lymphokine profile .Crit Rev Oncol Hematol ,2001,39 (1-2) : 125-132.
[14] Hamilton AJ , Baulcombe DC. A species of small antisense RNA in posttranscriptional gene silencing in plants . Science, 1999 ,286 (5441): 950-952.
[15] Hammond SM , Boettcher S , Caudy A A ,et al. Argonaute2 , a link between genetic and biochemical analyses of RNAi . Science , 2001 , 293 (5532) : 1146 - 1150.
[16] Elbashir SM , Lendeckel W, Tuschel T. RNA interference is mediated by 21- and 22-nucleotide RNAs[J ]. Genes Dev, 2001,15(2): 188-200.
[17] Phillip AS. RNA interference-2001. Genes Dev, 2001,15(5): 485-489.
[18] Hait NC, Oskeritzian CA,Paugh SW,et,al. Sphingosine kinases, sphingosine 1-phosphate, apoptosis and diseases. Biochim Biophys Acta. 2006,1758(12):2016-26.
[19] Maceyka M, Payne SG, Milstien S,et, al.Sphingosine kinase, sphingosine-l-phosphate,and apoptosis. Biochim Biophys Acta. 2002 ,1585 (2-3): 193-201.
[20] Cuvillier O. Sphingosine in apoptosis signaling. Biochim Biophys Acta. 2002,1585(2-3): 153-162.
[21] Alemany R, van Koppen CJ, Danneberg K,et,al. Regulation and functional roles of sphingosine kinases. Naunyn Schmiedebergs Arch Pharmacol. 2007,374(5-6): 413-28.
[22] Liu H, Chakravarty D, Maceyka M,et,al. Sphingosine kinases: a novel family of lipid kinases. Prog Nucleic Acid Res Mol Biol. 2002;71:493-511.
[23] Kohama T, Olivera A, Edsall L,et,al. Molecular cloning and functional characterization of murine sphingosine kinase.J Biol Chem. 1998 , 273(37): 23722-23728.
[24] Gulbins E. Regulation of death receptor signaling and apoptosis by ceramide J . Pharmacol Res, 2003,47(5):393 - 399.
[25] Victor E. Nava, Olivier Cuvillier, Lisa C. Edsall,et,al Sphingosine Enhances Apoptosis of Radiation-resistant Prostate Cancer Cells ,Cancer Res,2000, 60: 4468-4474.
[26] Dimitri Pchejetski,Muriel Golzio, Elisabeth Bonhoure,et,al.Sphingosine Kinase-1 as a Chemotherapy Sensor in Prostate Adenocarcinoma Cell and Mouse Models Cancer Res ,2005; 65: (24): 11667-11675.
[27] Kohama T, Olivera A, EdsallL, et al. Molecular cloning and functional characterization of murine sphingosine kinase .J Biol Chem, 1998, 273(37): 23722-23728.
[28] Jorgenson R. Altered gene exp ression in p lants due to trans interactions between homologous genes. Trends Biotechnol, 1990,8(12): 340 - 344.
[29] Cogoni C,Romano N ,Macino G.Suppression of gene expression homologos transgenes [J]Antonie Van Leeuwenhoek,1994,65(3):205-209.
[30] Guo S, Kemphues K J. Par21, a gene required for establishing polarity in C. elegans embryos, encodes a putative Ser/Thr kinase that is asymmetrically distributed . Cell,1995,81(4):611-620.
[31] Fire A, Xu S, MontgomeryM K, et al. Potent and specific genetic interference by double-stranded RNA in caenorhabditis elegans[ J ]. Nature, 1998, 391 (6669): 806 -11.
[32] William M, Winston, C M, Craig P H. Systemic RNAi in C.elegans Requires the Putative Transmembrane Protein SID-1 . Science, 2002,295(29):2456-2459.
[33] Lipardi C,Wei Q, Paterson BM.RNAi as random degradative PCR: siRNA primers convert mRNA into dsRNAs that are degraded to generate new siRNAs. Cell, 2001,107( 3): 297- 307.
[34] Garzon R, Pichiorri F, Palumbo T, et al. Micro RNA fingerprints during human megakaryocytopoiesis. PANS , 2006,103 (13): 5078- 5083.
[35] Horvitz HR, Sulston JE. Isolation and genetic characterization of cell-lineage mutants of the nematode caenorhnbditis elegans[ J ]. Genetics, 1980,96 (2): 435 - 454.
[36] Elbashir SM, LendeckelW, Tuschl T. RNA interference is mediated by 21 and 22 nueleotide RNAs . Genes Development, 2001, 15(2): 188 - 200.
[36] Hutvagner G, McLachlan J, PasquinelliAE, et al. A cellular functionof for the RNA-interference enzyme Dicer in the maturation of the let27small temporal RNA. Science, 2001,293 (5531): 834 - 838.
[37] Wu LG, Fan JH, Belasco JG. MicroRNAs direct rapid deadenylation of mRNA. PNAS , 2006,103 (11): 4034 - 4039.
[38] Ruts S, Scheffold A. Towards in vivo application of RNA interference new toy, old problems . Arthritis Res Ther,2004,6: 78 - 85.
[39] Elbashir SM, Harborth J, Lendeckel W, et al. Duplexes of 21-nucleotide RNAs mediate RNA interference in cultured mammalian cells . Nature,2001, 411(6836): 494-498.
[40] Bass BL.RNA interference.The short answer .Nature, 2001,411 (6836): 428- 429.
[41] Brake O, Berkhout B. Lentiviral vectors that carry anti-H IV shRNAs: problems and solutions. J GeneMed, 2007,9:743 - 750.
[42] Mizuguchi H, FunakoshiN, Hosono T, et al. Rapid construction of small interfering RNA-expressing adenoviral vectors on the basis of direct cloning of short hairp in RNA-coding DNAs. Hum Gene Ther, 2007,18: 74 - 80.
[43] Storvold GL, Gjernes E, Askautrud HA, et al. A retroviral vector for siRNA exp ression in mammalian cells . MolBiotechnol, 2007, 35: 275 - 282.
[44] Pchejetski D, Golzio M, Bonhoure E, et al.Sphingosine kinase-1 as a chemotherapy sensor in prostate adenocarcinoma cell and mouse models. Cancer Res. 2005 ,65(24): 11667-11675.
[45] Nava VE, Cuvillier O, Edsall LC, et al. Sphingosine enhances apoptosis of radiation-resistant prostate cancer cells. Cancer Res 2000,60,4468-4474.
[46] Bourbon NA ,Yun J ,Kester M. Ceramide directly activates protein kinase C zeta to regulate a stress-activated protein kinase signaling complex J Biol Chem ,2000,275 (45) :35617-356231
[47] Ruvolo PP. Intracellular signal transduction pathways activated by ceramide and its metabolites . Pharmacol Res ,2003 ,47 (5):383-392.
[48] Jarvis WD, Fornari FA J r ,Auer KL, et al.Coordinate regulation of stress and mintgen activated protein kinase in the apoptotic actions of ceramide and sphingosine. Mol Pharmacol ,1997 ,52 (6) :935947.
[49] Willaime S ,Vanhoutte P ,Caboche J , et al. Ceramide-induced apoptosis in cortical neurons is mediated by an increase in p38 phosphorylation and not by the decrease in ERK phosphorylation .Eur J Neurosci .2001,13 (11) :2037-2046
[50] Edsall LC, Spiegel S. Enzymatic measurement of sphingosine 1-phosphate. Anal Biochem 1999,272:80-6.
[51] Hla T. Signaling and biological actions of sphingosine 1-phosphate. Pharmacol Res. 2003; 47(5):401-407.
[52] Spiegel S, Milstien S, Functions of a new family of sphingosine -1-phosphate receptors. Biochim. Biophys. Acta .2000,1484:107-116
[53] Spiegel S, Milstien S. Sphingosine-1-phosphate: an enigmatic signaling lipid.Nat Rev Mol Cell Biol. 2003,4:397-407.
[54] Spiegel S, Milstien S, Sphingosine 1-phosphate, a key cell signaling moleculeJ Biol Chem 2002,277 :25851-25854.
[55] Cuvillier O, Pirianov G, Kleuser B, et al. Suppression of ceramide-mediated programmed cell death by sphingosine-1-phosphate. Nature, 1996, 381(6585): 800-803.
[57] Hideshima T, Nakamura N, Chauhan D, Anderson KC. Biologic sequelae of interleukin-6 induced PI3-K/Akt signaling in multiple myeloma. Oncogene .2001, 20:5991-6000.
[58] Podar K, Mostoslavsky G, Sattler M, et al. Critical role for hematopoietic cell kinase (Hck)-mediated phosphorylation of Gab1 and Gab2 docking proteins in interleukin 6-induced proliferation and survival of multiple myeloma cells. J Biol.Chem .2004 279:21658-65.
[59] Le Scolan E, Pchejetski D, Banno Y, et al. Overexpression of sphingosine kinasel is an oncogenic event in erythroleukemic progression. Blood. 2005 ,106(5): 1808-1816.
[60] Xia P, Gamble JR, Wang L, et al. An oncogenic role of sphingosine kinases . Curr Biol, 2000,10(23): 1527-1530.
[61] Olivera A, Spiegel S. Sphingosine-1-phosphate as second messenger in cell proliferation induced by PDGF and FCS mitogens. Nature (1993) 365:557-60.
[62] Pitson SM, Moretti PA, Zebol JR, et al. The nucleotide-binding site of human sphingosine kinase 1. J Biol Chem (2002) 277:49545-53.
[63] Wu W, Mosteller RD, Broek D. Sphingosine kinase protects lipopolysaccharide- activated macrophages from apoptosis. Mol Cell Biol (2004) 24: 7359-69.
[64] Bonhoure E, Pchejetski D, Aouali N, et al. Overcoming MDR-associated chemoresistance in HL-60 acute myeloid leukemia cells by targeting shingosine kinase-1.Leukemia .2005;[Epub ahead of print]
[65] Baltzer AW , Lattermann C , Whalen JD , et al . Genetic enhancenent of fracture repair : healing of an experimental sepmental defect by adenoviral transfer of the BMP-2 gene J . Gene Ther, 2000,7(9): 7342739.
[66] Baltzer AM , Lattermann C , Whalen JD , et al . Potential role of direct adenoviral gene transfer in enhancing fracture repair J . Clin Orthop , 2000 , ( 379 Suppl):S120-S125.
[67] Alden TD , Pittman DD , Hankins GR , et al. In vivo endochron dral bone formation using a bone morphogenetic protein 2 adenoviral vector[J ]. Hum Gene Ther, 1999,10(13): 224522253.
[68] Bergelson JM, Cunningham JA, Droguett G, et al. Isolation of common receptor for Coxsackie B viruses and adenoviruses 2 and 5 . Science, 1997, 275 (5304): 1320 -1323.
[69] Wickham TJ, Mathias P, Cheresh DA, et al. Integrins alpha beta 3 and alphav beta 5 promote adenovirus internalization not virus attachment. Cell, 1993, 73 (2) :309 -319.
[70] Bauerschmitz GJ, Barker SD, Hemminki A. Adenoviral gene therapy for cancer: from vectors to targeted and replication competent agents . Int J Oncol, 2002, 21 (6): 1161-1174.
[71] Wickham TJ, SegalDM, Roelvink PW, et al. Targeted adenovirus gene transfer to endothelial and smooth muscle cells by using bispecific antibodiesJ . J Virol, 1996,70 (10): 6831-6838.
[72] Watkins SJ, Mesyanzhinov VV, Kurochkina LP, et al. The 'adenobody' approach to viral targeting: specific and enhanced adenoviral gene delivery . Gene Ther, 1997,4(10): 1004-1012.
[73] Dmitriev I, Kashentseva E, Rogers BE, et al. Ectodomain of coxsackie virus and adenovirus recep tor genetically fused to epidermal growth factor mediates adenovirus targeting to epidermal growth factor receptor positive cells. J Virol, 2000, 74 (15) :6875 - 6884.
[74] HemminkiA, Dmitriev I, Liu B, et al. Targeting oncolytic adenoviral agents to the epidermal growth factor pathwaywith a secretory fusion molecule. Cancer Res, 2001,61 (17): 6377-6381.
[75] Ogretmen B, Hannun YA. Biologically active sphingolipids in cancer pathogenesis and treatment. Nat Rev Cancer .2004,4:604-616.
[76] Nava VE, Hobson JP, Murthy S,et al.Sphingosine kinase type 1 promotes estrogen-dependent tumorigenesis of breast cancer MCF-7 cells. Exp Cell Res. 2002,281:115-127.
[77] French KJ, Schrecengost RS, Lee BD, et al. Discovery and evaluation of inhibitors of human sphingosine kinase. Cancer Res 2003,63:5962-5969.
[78] Nava VE, Cuvillier O, Edsall LC, et al. Sphingosine enhances apoptosis of radiation-resistant prostate cancer cells. Cancer Res 2000,60,4468-4474.
[79] Liu H, Sugiura M, Nava VE, et al. Molecular cloning and functional characterization of a novel mammalian sphingosine kinase type 2 isoform [J]. Biol Chem, 2000, 275(26): 19513-20
[80] Spiegel s, Kolesnick R.Sphingosine 1-phosphate as a therapeutic agent. Leukemia. 2002 Sep: 16(9): 1596-602.
[81] Sadahira Y, Ruan F, Hakomori S, et al. Sphingosine 1-Phosphate, a Specific Endogenous Signaling Molecule Controlling Cell Motility and Tumor Cell Invasiveness. Proc. Natl. Acad. Sci. U.S.A. 1992, 89:9686-9690.
[82] Lee MJ, Van Brocklyn JR, Thangada S, et al. Sphingosine-1-Phosphate as a Ligand for the G Protein-Coupled Receptor EDG-1. Science, 1998, 279:1552-1555.
[83] Edsall LC, Cuvillier O, Twitty S, et al. .Sphingosine kinase expression regulates apoptosis and caspase activation in PC12 cells.J Neurochem.2001,76:1573-1584.
[84]Chang HC,Hsu C,Hsu HK,et al.Functional role of caspases in sphingosine-induced apoptosis in human hepatoma cells.IUBMB Life,2003,55(7):403-7.
[85]Craig R W.Mcl-1 provides a window on the role of the BCL-2 family in cell proliferation,differentiation and tunorigenesis.Leukemia.2002,16(5):444 - 454.
[86]Nijhawan D,Fang M,Traer E,et al.Elimination of Mcl-1 is required for t he initiation of apoptosis following ultraviolet irradiation.Genes Dev,2003,17(12):1475-1486.
[87]Dererme S,Monia B,Dean N M,et al.Antisense strategy shows that Mcl-1rather than Bcl-2 or Bcl2x(L) is an essential survival protein of human myeloma cells.Blood.2002,100(1):194 - 199.
[88]Zhang B,Gojo I,Fenton R G.Myeloid cell factor-1 is a critical survival factor for multiple myeloma.Blood,2002,99(6):1885 - 1893.
[89]Francesco Fabbril,Giovanni Brigliadoril,Silvia Carlonil,et al.Zoledronic acid increases docetaxel cytotoxicity through pMEK and Mcl-1 inhibition in a hormone-sensitive prostate carcinoma cell line.J Tran Med 2008,6(43):1-10.
[90]Cavarretta IT,Neuwirt H,Untergasser G,et al.The antiapoptotic effect of IL-6autocrine loop in a cellular model of advanced prostate cancer is mediated by Mcl-1.Oncogene.2007,26:2822-2832.
[91]Bernhard Gillissen,Frank Essmann,Philipp G,et al.Mcl-1 determines the Bax dependency of Nbk/Bik-induced apoptosis.J.Cell Biol.2007,179(4):701-715.
[92]Krajewski S,Bodrug S,Krajewski M,et al.Immunohistochemical analysis of Mcl-1 protein in human tissues.AmJ Pathol.1995,146(6):1309-1319.
[93]Craig RW.Mcl-1 provides a window on the role of the BCL2 family in cell proliferation differentiation and tumorigenesis.Leukemia(2002) 16:444-454.
[94]Le Gouill S,Podar K,Amiot M,et al.VEGF induces Mcl-1 up-regulation and protects multiple myeloma cells against apoptosis.Blood(2004) 104:2886-9
[95]Puthier D,Bataille R,Amiot M.IL-6 up-regulates mcl-1 in human myeloma cells through JAK / STAT rather than ras / MAP kinase pathway.Eur J Immunol.1999,29(12):3945-50.
[96]P.K.Epling-Burnette,Jin Hong Liu,Robyn Catlett-Falcone,et al.Inhibition of STAT3 signaling leads to apoptosis of leukemic large granular lymphocytes and decreased Mcl-1 expression.J.Clin.Invest.2001.107:351-362.
[97]Kuo ML,Chuang SE,Lin MT,et al.The involvement of PI 3-K/Akt-dependent up-regulation of Mcl-1 in the prevention of apoptosis of Hep3B cells by interleukin-6.Oncogene.2001;20(6):677-85.
[98]Jourdan M,Veyrune JL,Vos JD,et al.A major role for Mcl-1 antiapoptotic protein in the IL-6-induced survival of human myeloma cells.Oncogene.2003;22(19):2950-9.
[99]Sano J,Oguma K,Kano R,Hasegawa A.Molecular cloning of canine Mcl-1gene and its expression in tumor cell lines.J Vet Med Sci.2004;66(6):709-12.
[100]Johnston JB,Paul JT,Neufeld NJ,Haney N,Kropp DM,Hu X,Cheang M,Gibson SB.Role of myeloid cell factor-1(Mcl-1) in chronic lymphocytic leukemia.Leuk Lymphoma.2004;45(10):2017-27.
[101]Opferman JT,Letai A,Beard C,et al.Development and maintenance of B and T lymphocytes requires antiapoptotic MCL-1.Nature.2003;426(6967):671-6.
[102]Le Gouill S,Podar K,Amiot M,Hideshima T,Chauhan D,VEGF induces Mcl-lup-regulation and protects multiple myeloma cells against apoptosis.Blood.2004;104(9):2886-92..
[103]Derenne S,Monia B,Dean NM,et al.Antisense strategy shows that Mcl-1rather than Bcl-2 or Bcl-x(L) is an essential survival protein of human myeloma cells.Blood.2002;100:194-9.
[104]Leo CP,Hsu SY,Chun SY,Bae HW,Hsueh AJ.Characterization of the antiapoptotic Bcl-2 family member myeloid cell leukemia-1(Mcl-1) and the stimulation of its message by gonadotropins in the rat ovary.Endocrinology.1999;140:5469-77.
[105]Maryla K,Stanislaw K,Jonathan,IE,et al.Immunohistochemical Analysis of bcl-2,bax,bcl-X,and mcl-1 Expression in Prostate Cancers.Am J Pathol 1996,148(5):1567-1576.
[106] Li QF, Wu CT, Duan H.F, et,al. Activation of sphingosine kinase mediates suppressive effect of interleukin-6 on human multiple myeloma cell apoptosis. Br J Haematol .2007; 138 632-39.
[107] El-Zawahry A, McKillop J, Voelkel-Johnson C.Doxorubicin increases the effectiveness of Apo2L/TRADL for tumor growth inhibition of prostate cancer xenografts. BMC Cancer. 2005 ,7;5:2
[108] Kelly MM, Hoel BD, Voelkel-Johnson C Doxorubicin pretreatment sensitizes prostate cancer cell lines to TRAIL induced apoptosis which correlates with the loss of c-FLIP expression. Cancer Biol Ther. 2002; 1(5):528-9.
[109] Brusselmans K, De Schrijver E, Verhoeven G, et al . RNA interference-mediated silencing of the acetyl-CoA-carboxylase-alpha gene induces growth inhibition and apoptosis of prostate cancer cells. Cancer Res. 2005 , 65(15):6719-6725.
[110] Liao X, Tang S, Thrasher JB,et al. Small-interfering RNA-induced androgen receptor silencing leads to apoptotic cell death in prostate cancer. Mol Cancer Ther. 2005,4(4):505-515.
[111] Grzmil M, Thelen P, Hemmerlein B, et al.Bax inhibitor-1 is overexpressed in prostate cancer and its specific down-regulation by RNA interference leads to cell death in human prostate carcinoma cells. Am J Pathol. 2003,163(2):543-552
[112] Grzmil M, Thelen P, Hemmerlein B, et al.Bax inhibitor-1 is overexpressed in prostate cancer and its specific down-regulation by RNA interference leads to cell death in human prostate carcinoma cells. Am J Pathol. 2003,163(2):543-552
[113] De Schrijver E, Brusselmans K, Heyns W, et al.RNA interference-mediated silencing of the fatty acid synthase gene attenuates growth and induces morphological changes and apoptosis of LNCaP prostate cancer cells.Cancer Res. 2003 ,63 (13):3799-3804.
[114] Song J, Pang S, Lu Y, et al. Gene silencing in androgen-responsive prostate cancer cells from the tissue-specific prostate-specific antigen promoter. Cancer Res. 2004,64(21):7661-7663
[115] Brusselmans K, De Schrijver E, Verhoeven G, et al.RNA interference- mediated silencing of the acetyl-CoA-carboxylase-alpha gene induces growth inhibition and apoptosis of prostate cancer cells.Cancer Res.2005,65(15):6719-6725.
[116]Assikis VJ,Simons JW.Novel therapeutic strategies for androgen-independent prostate cancer:an update.Semin Oncol.2004,31:26-32.
[117]Cuvillier O,Sphingosine kinase-1 a potential therapeutic target in cancer.Anticancer Drugs 2007,18:105-110.
[118]Sabbadini R.A.Targeting sphingosine-1-phosphate for cancer therapy.Br J Cancer.2006;95:1131-1135.
[119]Ryo A,Uemura H,Ishiguro H,et al.Stable suppression of tumorigenicity by Pin1-targeted RNA interference in prostate cancer.Clin Cancer Res.2005,11(20):7523-7531
[120]Han B,Xie H,Chen Q,et al.Sensitizing hormone-refractory prostate cancer cells to drug treatment by targeting 14-3-3sigma.Mol Cancer Ther.2006,5(4):903-912.
[1] Jorgenson R. Altered gene exp ression in p lants due to trans interactions between homologous genes. Trends Biotechnol, 1990,8(12): 340 - 344.
[2] Cogoni C,Romano N ,Macino G.Suppression of gene expression homologos transgenes [J]Antonie Van Leeuwenhoek,1994,65(3):205-209.
[3] Guo S, Kemphues K J. Par21, a gene required for establishing polarity in C. elegans embryos, encodes a putative Ser/Thr kinase that is asymmetrically distributed . Cell,1995,81(4):611-620.
[4] Fire A, Xu S, MontgomeryM K, et al. Potent and specific genetic interference by double-stranded RNA in caenorhabditis elegans[ J ]. Nature, 1998, 391 (6669) : 806 -11.
[5] William M, Winston, C M, Craig P H. Systemic RNAi in C.elegans Requires the Putative Transmembrane Protein SID-1. Science, 2002,295(29):2456-2459.
[6] Garzon R, Pichiorri F, Palumbo T, et al. Micro RNA fingerprints during human megakaryocytopoiesis. PANS , 2006,103 (13): 5078- 5083.
[7] Horvitz HR, Sulston JE. Isolation and genetic characterization of cell-lineage mutants of the nematode caenorhnbditis elegans[ J ]. Genetics, 1980,96 (2): 435 - 454.
[8] Elbashir SM, LendeckelW, Tuschl T. RNA interference is mediated by 21 and 22 nueleotide RNAs . Genes Development, 2001,15(2): 188 - 200.
[9] Hutvagner G, McLachlan J, PasquinelliAE, et al. A cellular functionof for the RNA-interference enzyme Dicer in the maturation of the let27 small temporal RNA. Science, 2001,293 (5531): 834 - 838.
[10] Wu LG, Fan JH, Belasco JG. MicroRNAs direct rapid deadenylation of mRNA. PNAS , 2006,103 (11): 4034 - 4039.
[11] Buratowski S, Moazed D. Gene regulation: Expression and silencing coupled. Nature, 2005,435 (7046): 1174 -1175.
[12] Elbashir SM, Harborth J, Lendeckel W, et al. Duplexes of 21-nueleotide RNAs mediate RNA interference in cultured mammalian cells . Nature,2001, 411(6836): 494-498.
[13]Bass BL.RNA interference.The short answer.Nature,2001,411(6836):428-429.
[14]Sioud M.Therapeutic siRNAs[J].Trends Pharmacol Sci,2004,25(1):22-28.
[15]Elbashir SM,Harborth J,Lendeckel W,et al.Duplexes of 21-nu-cleotide RNAs mediate RNA interference in cultured mammalian cells[J].Nature,2001,411:428 - 429.
[16]Bernard D,Pourtier - Manzanedo A,Gil J,et al.Myc confers androgen -independent prostate cancer cell growth.J Clin Invest,2003,112(11):1724-1731.
[17]Lee SO,Lou W,Qureshi KM,et al.RNA interference targeting Stat3 inhibits growth and induces apoptosis of human prostate cancer cells.Prostate,2004,60(4):303-309.
[18]Grzmil M,Thelen P,Hemmerlein B,et al.Bax inhibitor - 1 is overexpressed in prostate cancer and its specific down - regulation by RNA interference leads to cell death in human prostate carcinoma cells.Am J Patho1,2003,163(2):543 - 552.
[19]Brummelkamp TR,Bemards R.New tools for functional animal cancer genetics[J].Nat Rev Cancer,2003,3:781 - 791.
[20]Hannon GJ,Rossi J.Unlocking the potential of the human genome with RNA interference[J].Nature,2004,431:371 - 378.
[1] Leung R, Paul A. RNA interference: from gene silencing to gene- specific therapeutics. Pharmacology & Therapeutics, 2005,107:222 - 239.
[2]Eastham JA, Grafton W, Martin CM. et al. Suppression of primary tumor growth and the progression to metastasis with p53 adenovirus in human prostate cancer. J Urol 2000;164(3 Pt 1): 814-819.
[3] Harrington KJ ,Spitzweg C ,Bateman AR ,et al . Gene therapy for prostate cancer: current status and future prospects J Urol ,2001; 166(4) :1220- 1233
[4] Bernard D ,Pourtier - Manzanedo A ,Gil J ,et al .Myc confers androgen -independent prostate cancer cell growth. J Clin Invest ,2003 ,112(11):1724-1731.
[5] Lee SO ,Lou W,Qureshi KM,et al . RNA interference targeting Stat3 inhibits growth and induces apoptosis of human prostate cancer cells.Prostate ,2004 , 60(4):303-309.
[6]Grzmil M.Thelen P ,Hemmerlein B ,et al. Bax inhibitor - 1 is overexpressed in prostate cancer and its specific down - regulation by RNA interference leads to cell death in human prostate carcinoma cells. Am J Pathol ,2003 ,163 (2) :543 - 552.
[7] Tan C, Cruet - Hennequart S, Troussard A, et al. Regulation of tumor angiogenesis by integrin linked kinase(ILK). Cancer Cell, 2004,5(1):79-90.
[8]Mincheff M,Altankova I , Zoubak S et al . In vivo transfection and/ or coss-riming of dendritic cells following DNA and adenoviral immunizations for immunotheraphy of cancer changes in peripheral mononuclearsubsets and intracellular IL-4 and IFN-gamma lymphokine profile [J ] .Crit Rev Oncol Hematol ,2001,39 (1-2):125-132.
[9]Ohanian J , Ohanian V. Sphingolipids in mammalian cell signalling.[J].Cell Mol Life Sci, 2001,58 (14) : 2053- 2068.
[10] Hait NC, Oskeritzian CA,Paugh SW,et,al. Sphingosine kinases, sphingosine 1-phosphate, apoptosis and diseases. Biochim Biophys Acta. 2006,1758(12):2016-26.
[11]Maceyka M, Payne SG, Milstien S,et, al.Sphingosine kinase,sphingosine- 1-phosphate,and apoptosis. Biochim Biophys Acta. 2002,1585(2-3): 193-201.
[12]Cuvillier O. Sphingosine in apoptosis signaling._Biochim Biophys Acta. 2002 ,1585(2-3): 153-162.
[13]Alemany R, van Koppen CJ, Danneberg K,et,al. Regulation and functional roles of sphingosine kinases. Naunyn Schmiedebergs Arch Pharmacol. 2007,374 (5-6):413-28.
[14] Liu H, Chakravarty D, Maceyka M,et,al. Sphingosine kinases: a novel family of lipid kinases. Prog Nucleic Acid Res Mol Biol. 2002;71:493-511.
[15]Kohama T, Olivera A, Edsall L,et,al. Molecular cloning and functional characterization of murine sphingosine kinase.[J]J Biol Chem. 1998 , 273(37): 23722-23728.
[16]Gulbins E. Regulation of death receptor signaling and apoptosis by ceramide[ J ]. Pharmacol Res, 2003,47(5):393 - 399.
[17] Edsall LC, Cuvillier O, Twitty S, et al. Sphingosine kinase expression regulates apoptosis and caspase activation in PC 12 cells [J]. Neurochem, 2001, 76(5): 1573-84.
[18] Chang HC, Hsu C, Hsu HK, et al. Functional role of caspases in sphingosine-induced apoptosis in human hepatoma cells [J]. IUBMB Life, 2003, 55(7): 403-7.
[19]Xia P, Gamble JR, WangL, et al. An oncogenic role of sphingosine kinase[ J ]. Curr Biol, 2000,10 (23): 1527 -1530.
[20] Olivera A, Kohama T, Edsall L, et al. Sphingosine kinase expression increases intracellular sphingosine-1-phosphate and promotes cell growth and survival [ J ]. J Cell Biol, 1999,147 (3 ) :545 - 558.
[21]Victor E. Nava, Olivier Cuvillier, Lisa C. Edsall,et,al Sphingosine Enhances Apoptosis of Radiation-resistant Prostate Cancer Cells ,Cancer Res,2000,60:4468-4474.
[22]Dimitri Pchejetski,Muriel Golzio, Elisabeth Bonhoure,et,al Sphingosine Kinase-1 as a Chemotherapy Sensor in Prostate Adenocarcinoma Cell and Mouse Models Cancer Res ,2005; 65: (24):11667-11675.