RNAi沉默survivin基因对TCCB的影响及其机制的研究
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摘要
目的筛选和鉴定重组表达质粒pshRNA-survivin。
方法重新克隆pshRNA-survivin重组质粒后,Amp筛选阳性克隆提取质粒DNA,用Sal I、EcoR I和Hind III分别酶切阳性克隆,并用相同的条件酶切载体pTZU6+1作为对照,1%琼脂糖凝胶电泳鉴定;将筛选的阳性克隆质粒进行序列分析。
结果经EcoR I和Hind III双酶切和序列分析证实阳性克隆中含有和设计片段完全一致的序列,插入DNA片段为:TCGAGCTGAGAACGAGCCAGACTTGTTAGTACTCAAGTCTGGCTCGTTCTCAGTTTTT(SUR-siRNA suqunce),所得测序结果与GeneBank文献报道的一致,未见缺失和突变,表明成功筛选和鉴定了含目的DNA片段的重组质粒pshRNA-survivin。
结论重组质粒pshRNA-survivin筛选和鉴定成功,可用于后续实验。
目的观察重组质粒pshRNA-survivin对TCCB细胞株T24细胞中survivin基因和蛋白表达的抑制作用。
方法将pshRNA-survivin质粒转染TCCB细胞株T24细胞,采用RT-PCR和Western blot检测T24细胞内survivin基因和蛋白的表达。
结果pshRNA-survivin转染T24细胞后,能明显抑制survivin基因和蛋白的表达,应用Quantity One软件分析结果,survivin mRNA表达抑制率达61.73%,survivin蛋白表达抑制率达53.37%。
结论pshRNA-survivin能够抑制T24细胞survivin基因和蛋白的表达。
目的观察pshRNA-survivin对T24细胞的生物学行为的影响。
方法pshRNA-survivin质粒转染TCCB细胞株T24细胞,MTT法观察pshRNA-survivin对细胞的增殖抑制作用;细胞运动实验、细胞侵袭实验检测psh-survivin对T24细胞的生长、运动、侵袭的抑制作用;流式细胞仪和AO/EB荧光染色法检测T24细胞的凋亡;透射电镜观察T24细胞超微结构变化。
结果MTT结果显示,转染组在24h、48h、72h时肿瘤抑制率分别为15.69%、27.64%和59.13%,细胞增殖受到抑制;流式细胞结果表明pshRNA-survivin组的细胞凋亡率为(16.76±1.31)%,与未转染组凋亡率(2.82±1.44)%、空载体组凋亡率(3.59±1.23)%比较有显著差异(P<0.01);AO/EB荧光染色法测定转染24h后,未转染组凋亡率为(2.37±1.67)%,空载体组的凋亡率为(5.15±2.28)%,pshRNA-survivin组的细胞凋亡率为(14.26±2.97)%,转染组与未转染组、空载体组相比较有显著性差异(P<0.01),转染48h后,转染组细胞死亡率(40.03±6.32)%和其他两组比较差异有显著性(P<0.01);细胞运动实验、细胞侵袭实验表明pshRNA-survivin组的细胞侵袭力与运动能力均有显著的降低(穿膜细胞数分别为10.34±1.85、41.32±3.47),与未转染组(27.62±2.06、62.84±4.97)和空载体组(26.07±1.73、64.15±6.71)比较有显著差异(P<0.01);透射电镜可观察到pshRNA-survivin组发生大量T24细胞的凋亡。
结论当沉默survivin基因后,T24细胞增殖受到抑制、细胞侵袭力与运动能力均有明显的下降,细胞凋亡增加,提示survivin可能是TCCB生物学治疗的一个潜在靶点。
目的建立TCCB裸鼠异位肿瘤模型,观察pshRNA-survivin对TCCB生长抑制作用。
方法筛选稳定表达survivin-siRNA的膀胱移行细胞癌细胞株(T24/survivin-siRNA);实验共分3组:pshRNA-survivin转染组、空载体组、未转染组(每组5只);建立裸鼠皮下种植瘤模型,观察肿瘤形成时间,计算抑瘤率;HE染色行组织学检查;免疫组化检测survivin蛋白表达。
结果pshRNA-survivin组种植瘤形成的时间显著地延长,与其它两组比较有显著性差异(P<0.01);在14d、21d,pshRNA-survivin组种植瘤体积(分别为54.19±3.81、149.54±11.49),与未转染组(138.40±12.44、311.02±37.01)和空载体组(167.15±13.15、338.24±19.62)比较有显著性差异(P<0.01);pshRNA-survivin组21d时的抑瘤率为68.93%,与未转染组、空载体组有明显差异(P<0.01);光镜下可见未转染组和空载体组发生肌肉侵润、肌纤维的溶解、断裂;免疫组化显示pshRNA-survivin组survivin蛋白的表达与未转染组比较有显著的降低(IOD分别为8705.4、3814932.1)。
结论在TCCB裸鼠异位肿瘤模型中,pshRNA-survivin能够显著抑制移植瘤的生长、浸润和survivin蛋白的表达。
Objective To identified the plasmid containing short hairpin RNA(shRNA)of survivin .
Methods PshRNA-survivin expression plasmid get from Dr Huang Ai-long;pshRNA-survivin was emplified in system and identitified by enzyme digestion and sequencing method.
Results The recombinant plasmid pshRNA-survivin was identified successfully by enzyme digestion and sequencing.
Conclusion The results show that the short hairpin RNA of survivin can be efficiently identified.
Objective To observe the plasmid containing short hairpin RNA(shRNA)of survivin suppressed the expression of exogenous survivin gene in T24 cells.
Methods The plasmid pshRNA-survivin was stably transfected into TCCB cells T24 to detect effect of survivin expression and analyze the inhibition of survivin gene with semi-quantitative reverse transcriptase-polymerase chain reaction (RT-PCR) and western blot. Results The expression of surviving in transfected T24 cells was markedly depressed at both mRNA and protein levels (61.73%, 53.37%, respectively) as compared with control.
Conclusion The results showed that down-regulate the expression of survivin with RNA interference technology can significantly suppress expression of survivin to a certain degree.
Objective To assess the effects of pshRNA-survivin on the biological behaviors of T24 cells by gene siliencing.
Methods The biological effects were observed, including anchorage-independent growth by MTT method, and the effects of apoptosis inducing on T24 cells were detected by flow cytometry assay and comfired by electron microscope, the ability of mobility and invasion in vitro by cell migration assay and tranwell chamber assay.
Results The growth of tumor cells was retared by anchorage-independent growth assay. The inhibitory percentages of T24 cells of the experimental groups correlated with the negative control groups were 15.69%、27.64%、59.13% in 24hour、48hour and 72hour, respectively. Meanwhile, 24h after transfection, it was observed that silencing survivin by RNAi could significantly induce the spontaneous apoptosis of T24 cells at the rate 16.76±1.31%, detected by flow cytometry assay and comfirmed by electron microscope. In addition, fewer penetrating cells of pshRNA-survivin group were observed along with a marked inhibition of invasion by tranwell chamber assay (27.62±2.06,26.07±1.73,10.34±1.85*, respectively).
Conclusion The results showed that blocking the expression of survivin with RNA interference technology can significantly suppress expression of proliferation,mobility and invasion of T24 cells, and induce apoptosis to a certain degree. RNAi targeted to survivin has a potential value in gene therapy of bladder cancer.
Objective To observe the effects of pshRNA-Survivin on human bladder cancer T24 cell line and to suppress the expression of survivin gene in the animal model of BALB/c xenograft tumor.
Methods Establishment of TCCB T24 lines with expressing siRNA-survivin stably. Then T24 cells were inoculated into the right-back legs of BALB/c nude mice to establish bladder cancer model. The inhibitory effects were observed on the growth of tumor and analyzed the inhibition of survivin gene with SABC of immunohistochemistry; Microscope were used to observe the morphological changes.
Results Nude mice were injected subcutaneously with siRNA-survivin cells and xenograft tumor formed 17.0 days later,no subcutaneous metastasis.While the other two groups formed tumor at 12.4days,11.8days,respectively,six/all with subcutaneous metastasis.Tumor size were measured with caliper every seven days.21days after formed xenograft tumor,mice were sacrificed and their tumors were weighted for evaluative antitumor ratio.Result showed that the volume of T24/ siRNA-survivin xenografts in mice was effectively inhibited by pshRNA-survivin.The Ratio of antitumor was significantly higher in pshRNA-survivin group than those in control groups. The expression of survivin in pshRNA-survivin group in vivo was markedly depressed as compared.
Conclusion pshRNA-survivin exerts its antitumor effect on human bladder cancer T24 cell lines in vivo. The mechanisms may be changing tumor cell cycle and inducing tumor cell apoptosis by down-regulating the expression of survivin.
方法重新克隆pshRNA-survivin重组质粒后,Amp筛选阳性克隆提取质粒DNA,用Sal I、EcoR I和Hind III分别酶切阳性克隆,并用相同的条件酶切载体pTZU6+1作为对照,1%琼脂糖凝胶电泳鉴定;将筛选的阳性克隆质粒进行序列分析。
结果经EcoR I和Hind III双酶切和序列分析证实阳性克隆中含有和设计片段完全一致的序列,插入DNA片段为:TCGAGCTGAGAACGAGCCAGACTTGTTAGTACTCAAGTCTGGCTCGTTCTCAGTTTTT(SUR-siRNA suqunce),所得测序结果与GeneBank文献报道的一致,未见缺失和突变,表明成功筛选和鉴定了含目的DNA片段的重组质粒pshRNA-survivin。
结论重组质粒pshRNA-survivin筛选和鉴定成功,可用于后续实验。
目的观察重组质粒pshRNA-survivin对TCCB细胞株T24细胞中survivin基因和蛋白表达的抑制作用。
方法将pshRNA-survivin质粒转染TCCB细胞株T24细胞,采用RT-PCR和Western blot检测T24细胞内survivin基因和蛋白的表达。
结果pshRNA-survivin转染T24细胞后,能明显抑制survivin基因和蛋白的表达,应用Quantity One软件分析结果,survivin mRNA表达抑制率达61.73%,survivin蛋白表达抑制率达53.37%。
结论pshRNA-survivin能够抑制T24细胞survivin基因和蛋白的表达。
目的观察pshRNA-survivin对T24细胞的生物学行为的影响。
方法pshRNA-survivin质粒转染TCCB细胞株T24细胞,MTT法观察pshRNA-survivin对细胞的增殖抑制作用;细胞运动实验、细胞侵袭实验检测psh-survivin对T24细胞的生长、运动、侵袭的抑制作用;流式细胞仪和AO/EB荧光染色法检测T24细胞的凋亡;透射电镜观察T24细胞超微结构变化。
结果MTT结果显示,转染组在24h、48h、72h时肿瘤抑制率分别为15.69%、27.64%和59.13%,细胞增殖受到抑制;流式细胞结果表明pshRNA-survivin组的细胞凋亡率为(16.76±1.31)%,与未转染组凋亡率(2.82±1.44)%、空载体组凋亡率(3.59±1.23)%比较有显著差异(P<0.01);AO/EB荧光染色法测定转染24h后,未转染组凋亡率为(2.37±1.67)%,空载体组的凋亡率为(5.15±2.28)%,pshRNA-survivin组的细胞凋亡率为(14.26±2.97)%,转染组与未转染组、空载体组相比较有显著性差异(P<0.01),转染48h后,转染组细胞死亡率(40.03±6.32)%和其他两组比较差异有显著性(P<0.01);细胞运动实验、细胞侵袭实验表明pshRNA-survivin组的细胞侵袭力与运动能力均有显著的降低(穿膜细胞数分别为10.34±1.85、41.32±3.47),与未转染组(27.62±2.06、62.84±4.97)和空载体组(26.07±1.73、64.15±6.71)比较有显著差异(P<0.01);透射电镜可观察到pshRNA-survivin组发生大量T24细胞的凋亡。
结论当沉默survivin基因后,T24细胞增殖受到抑制、细胞侵袭力与运动能力均有明显的下降,细胞凋亡增加,提示survivin可能是TCCB生物学治疗的一个潜在靶点。
目的建立TCCB裸鼠异位肿瘤模型,观察pshRNA-survivin对TCCB生长抑制作用。
方法筛选稳定表达survivin-siRNA的膀胱移行细胞癌细胞株(T24/survivin-siRNA);实验共分3组:pshRNA-survivin转染组、空载体组、未转染组(每组5只);建立裸鼠皮下种植瘤模型,观察肿瘤形成时间,计算抑瘤率;HE染色行组织学检查;免疫组化检测survivin蛋白表达。
结果pshRNA-survivin组种植瘤形成的时间显著地延长,与其它两组比较有显著性差异(P<0.01);在14d、21d,pshRNA-survivin组种植瘤体积(分别为54.19±3.81、149.54±11.49),与未转染组(138.40±12.44、311.02±37.01)和空载体组(167.15±13.15、338.24±19.62)比较有显著性差异(P<0.01);pshRNA-survivin组21d时的抑瘤率为68.93%,与未转染组、空载体组有明显差异(P<0.01);光镜下可见未转染组和空载体组发生肌肉侵润、肌纤维的溶解、断裂;免疫组化显示pshRNA-survivin组survivin蛋白的表达与未转染组比较有显著的降低(IOD分别为8705.4、3814932.1)。
结论在TCCB裸鼠异位肿瘤模型中,pshRNA-survivin能够显著抑制移植瘤的生长、浸润和survivin蛋白的表达。
Objective To identified the plasmid containing short hairpin RNA(shRNA)of survivin .
Methods PshRNA-survivin expression plasmid get from Dr Huang Ai-long;pshRNA-survivin was emplified in system and identitified by enzyme digestion and sequencing method.
Results The recombinant plasmid pshRNA-survivin was identified successfully by enzyme digestion and sequencing.
Conclusion The results show that the short hairpin RNA of survivin can be efficiently identified.
Objective To observe the plasmid containing short hairpin RNA(shRNA)of survivin suppressed the expression of exogenous survivin gene in T24 cells.
Methods The plasmid pshRNA-survivin was stably transfected into TCCB cells T24 to detect effect of survivin expression and analyze the inhibition of survivin gene with semi-quantitative reverse transcriptase-polymerase chain reaction (RT-PCR) and western blot. Results The expression of surviving in transfected T24 cells was markedly depressed at both mRNA and protein levels (61.73%, 53.37%, respectively) as compared with control.
Conclusion The results showed that down-regulate the expression of survivin with RNA interference technology can significantly suppress expression of survivin to a certain degree.
Objective To assess the effects of pshRNA-survivin on the biological behaviors of T24 cells by gene siliencing.
Methods The biological effects were observed, including anchorage-independent growth by MTT method, and the effects of apoptosis inducing on T24 cells were detected by flow cytometry assay and comfired by electron microscope, the ability of mobility and invasion in vitro by cell migration assay and tranwell chamber assay.
Results The growth of tumor cells was retared by anchorage-independent growth assay. The inhibitory percentages of T24 cells of the experimental groups correlated with the negative control groups were 15.69%、27.64%、59.13% in 24hour、48hour and 72hour, respectively. Meanwhile, 24h after transfection, it was observed that silencing survivin by RNAi could significantly induce the spontaneous apoptosis of T24 cells at the rate 16.76±1.31%, detected by flow cytometry assay and comfirmed by electron microscope. In addition, fewer penetrating cells of pshRNA-survivin group were observed along with a marked inhibition of invasion by tranwell chamber assay (27.62±2.06,26.07±1.73,10.34±1.85*, respectively).
Conclusion The results showed that blocking the expression of survivin with RNA interference technology can significantly suppress expression of proliferation,mobility and invasion of T24 cells, and induce apoptosis to a certain degree. RNAi targeted to survivin has a potential value in gene therapy of bladder cancer.
Objective To observe the effects of pshRNA-Survivin on human bladder cancer T24 cell line and to suppress the expression of survivin gene in the animal model of BALB/c xenograft tumor.
Methods Establishment of TCCB T24 lines with expressing siRNA-survivin stably. Then T24 cells were inoculated into the right-back legs of BALB/c nude mice to establish bladder cancer model. The inhibitory effects were observed on the growth of tumor and analyzed the inhibition of survivin gene with SABC of immunohistochemistry; Microscope were used to observe the morphological changes.
Results Nude mice were injected subcutaneously with siRNA-survivin cells and xenograft tumor formed 17.0 days later,no subcutaneous metastasis.While the other two groups formed tumor at 12.4days,11.8days,respectively,six/all with subcutaneous metastasis.Tumor size were measured with caliper every seven days.21days after formed xenograft tumor,mice were sacrificed and their tumors were weighted for evaluative antitumor ratio.Result showed that the volume of T24/ siRNA-survivin xenografts in mice was effectively inhibited by pshRNA-survivin.The Ratio of antitumor was significantly higher in pshRNA-survivin group than those in control groups. The expression of survivin in pshRNA-survivin group in vivo was markedly depressed as compared.
Conclusion pshRNA-survivin exerts its antitumor effect on human bladder cancer T24 cell lines in vivo. The mechanisms may be changing tumor cell cycle and inducing tumor cell apoptosis by down-regulating the expression of survivin.
引文
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[3] Shariat SF,Casella R,Khoddami SM,et al.Urine detection of survivin is a sensitive marker for the noninvasive diagnosis of bladder cancer [J].J Urol,2004;171(2):626-630.
[4] Albini A,Iwamoto Y,Kleinman HK,et al.A rapid in vitro assay for quantitating the invasive potential of tumor cells.Cancer Res,1987;47(12):3239-3245.
[5] Mallo GV,Soubeyran P. Expression of Cdx1 and Cdx2 homeotic genes to leads to reduced malignancy in colon cancer derived cells.J Bio Chem,1998,273(22):1430-1436.
[6] 韩锐, 主编.抗癌药物研究与实验技术.北京:北京医科大学、协和医科大学联合出版社,1997,353-354.
[7] 曹贵华,吴小候,张尧,等. 膀胱癌患者尿脱落细胞存活素表达的临床意义. 中华泌尿外科杂志,2004;25(6):377-379.
[8] Kleiman H,McGarvey M,Hassell J,et al. Basement membrane complexes with biological activity.Biochemistry,1986,25(2):312-318.
[9] Repesh LA.A new in vitro assay for quantitation tumor cell invasion. Invasion Metast,1989; 9(3):192-208.
[10] Grimstad IA.Direct evidence that cancer cell locomotion contributes importantly to invasion. Exp Cell Res, 1987;173(2):515-523.
[11] Vicente A,Torres JC,Tapia DA et a1.E-Cadherin Is Required for Caveolin-1-Mediated Down-Regulation of the Inhibitor of Apoptosis Protein Survivin via Reduced β-Catenin-Tcf/Lef-Dependent Transcription. Mol Cell Biol,2007;27(21): 7703–7717.
[12] Vicente A, Torres JC, Tapia DA, et a1. Caveolin-1 controls cell proliferation and cell death by suppressing expression of the inhibitor of apoptosis protein surviving. Journal of Cell Science, 2006;119(11), 1812-1823 .
[1] Nasu S, Yagihashi A,Izawa, et al.Survivin mRNA expression in patients with breast cancer. Anticancer Res 2002; 22:1839-1842.12
[2] Vleminckx K,Vakaet L,Mareel M,et al.Genetic manipulation of E-cadherin expression by epithelial tumour cells reveals an invasion suppressor role.Cell,1991;66(1):10-109.13
[3] Gammallo C,Palacios J,Moreno G,et al.Beta-catenin expression pattern in stage Ⅰa ndⅡ ovarian cancinomas:relationship with beta-catenin gene mutations.Clinicopathological feature,and clinical outcome.Am J Pathol,1999,155(2):527-536.14
[4] Cui J,Zhou XD,Liu YK,et al.Mutation and overexpression of the beta-catenin gene may play an important role in primary hepatocellular carcinoma among Chinese people.J Cancer Res Clin Oncol,2001;127(9):577-581. 15
[5] 郑清友,靳风烁.凋亡抑制因子 survivin 在膀胱移行细胞癌中的表达及意义[J]. 第三军医大学学报 2005;27(l0):1030-1032.16
[6] Fukuda S, Pelus LM.Regulation of the inhibitor-of-apoptosis family member Survivin in normal cord blood and bone marrow CD34 cells by hematopoietic growth factor:implication of Survivin expression in normal hematopoiesis.Blood, 2001;98:2091-2100. 17
[7] Seliger B,Cabrera T,Garrido F,et al.HLA class I antigen abnormalities and immune escape by malignant cells.Semin Cancer Biol,2002;12:3-13.18
[8] Kren L,Brazdil J,Hermanova M,et al.Prognostic significance of anti-apoptosis proteins surviving and bcl-2 in non-small cell lung carcinomas:a clinical pathologic study of 102 cases. Appl Immunohistochem Mol Morphol, 2004;12(1):44-49.
[9] Cao C,Mu Y,Hallahan DE,et al.XIAP and surviving as therapeutic targets for radiation sensitization in preclinical models of lung cancer .Oncogen,2004;23(42):7047-7052.
[10] Blanc OP,Yu J,Simosa H,et al.Inhibitor of apoptosis protein Survivin regulates vascular injury.Nat Med,2002;8:987-994.
[11] Krysan K,Dalwadi H,Sharma S,et al.Cyclooxygenase 2-dependent expression of surviving is critical for apoptosis resistance in non-small cell lung cancer.Cancer Res,2004;64(18):6359-6362.
[1] Ambrosini G, AItieri DC, et al. A nevel anti-apoptosisgene, Survivn, expressed in cancer and lymphoma[J]. Nature MED,1997;3:917-921.
[2] Badran A, yoshida A, Ishikawa K, et al, Identification of anovel splice variant of the human anti-apoptopsis gene surviving[J]. Biochem Biophys Res Commum,2004;314(3):902.
[3] Uren A G, Wang l. Pakusch M, et al. Survivin and the inner centromere protein INCENP show similar cell-cycle localization and gene knockout phenotype[J]. Curr Biol,2002;10(21):1319.
[4] Deveraux QL, Reed JC. IAP family proteins- suppressors of apoptosis[J].Genes, 1999; 13 (3): 239 -252.
[5] Suzuki A, Hayashida M, Ito T, et al, Survivin initiates cell cycle entry by the complex activation with CDK4 /p16(INK4a)and CDK2, cyclinE complex activation[J]. Oncogene. 2000; 19(29): 3225-3234.
[6] Suzuki A, Ito T, Kawano H, et al, Suevivin initiates procaspase/P21 complex formation as a result of interaction with CDK4 to resist FAS-mediated cell death[J].Oncogene,2000; 19(10):1346-1353.
[7] Wheatley SP, Kandels L, Adams RR, et al. INCENP binds directly to tubulin, and requires dynamic microtubules to target to the cleavage furrow[J]. Exp, Cell Res,2001b;262:122-127.
[8] Oconnor DS, Schechner JS, Adida C, et al. Angioptosis during angiogenesis by surviving express in endothelial cell[J].Am J Pathol,2000;156(6):393.
[9] Papapetropoulos A, Fulton D, Mubboubi K, et al. Angiopioetin-1 inhibits endothelial cell[J]. J Biol Chem, 2000;275(13):9102.
[10] Alticri DC. Validating surviving as a cancer therapeutic target[J]. Nat.Rev. Cancer,2003;3:46-54.
[11] O'Connor D S, Schechner J S, Adida C. Control of apoptosis during angiogenesis by Survivin expression in endothelial cells[J].Am J Pathol,2000; 156(2): 393-398.
[12] Lu CD, Altieri DC. Tanigawa N. Expression of a novel anti-apoptosis gene, Survivin, correlated with tumor cell apoptosis and P53 accumulation in gastric carcinomas[J]. Cancer Res,1998;58(9):1808.
[13] Endoh A, Asanuma K, Moriai R, et al. Expression of surviving mRNA in CD34-positive cells[J]. Clin Chim AcTa,2001;306:149-151.
[14] Kawasaki H, Altieri DC, LuCD, et al. Unhibition of apoptosis by Survivin predicts Shorter Survivin rates in colorectal cancer[J].Cancer Res,1998;56(22):5071.
[15] Swana HS, Grossman D, Anthony JN, et al. Tumor content of the anti-apoplosis molecule Survivin and recurrence of bladder cancer[J]. N Engl J MED,1999;341:452-453.
[16] ZHANG Xiang-yang, ZENG Qiang, QI Fan,et al. Expression of Survivin protein in prostate cancer and its clinical sign ificance[J]. China Journl Of Modern Medicine, 2006;16:1060-1062.
[17] Mono M, Rosell R, Felip E, et al. A novel anti-apoptosis gene Rexpression of Survivin messenger RNA as a prognosis marker in nonsmall-cell lung cancers[J]. J Clin Oncol. 1999; 17: 2100-2104.
[18] Hou Yan, Hu Qun, Liu Aiguo, Zhang Liuqing, et al. Expression of survivin and its location in cell and clinical significance in pediatric acute leukemia[J]. Journal Of China PediaTric Blood And Cancer, 2006; 1:6-8.
[19] Smith SD, Wheeler MA, Plescia J, et al. Urine detection of Survivin and diagnosis of bladder cancer[J]. JAMA, 2001;17; 285(3):324-8.
[20] Ansell SM, Arendt BK, Grote DM. Inhibition of surviving expression suppresses the growth of aggressive non-hodgkin’s lymphoma[J].Leukemia,2004; 18(3):616-623.
[21] Fonaro M, Plescia J, Chheng S, et al. Fibronectin protects prostate cancer cells from tumor mecrosisi factor-alpha induced apoptosisi via the AKT/surviving pathway[J]. J boil chem, 2003;278(50):50402-50411.
[22] Fire A, Xu S, Montgomery MK, et al. Potent and specific genetic interference by double-stranded RNA in Caenorhabditis elegans[J].Nature,1998;391(6669):806-811.
[23] Kappler M, Bache M, Bartel F, et al. Knockdown of survivin expression by small interfering RNA reduces the clonogenic surviving of human sarcoma cell lines independentlyof p53[J]. Cancer Gene Ther, 2004; 11(3): 186-193.
[24] Marzia P, Mara B, Micheiandrea DC. Ribozyme-mediated down-regulation of surviving expression sensitizes human melanoma cells to potecan in vitro and in[J]. Carcinogenesis, 2004;10(5):1093.
[25] Jiangguo W, Xiang L, Dalin P, et al. Molecular Mechanism of inhibition of surviving transcription by the GC-rich sequence-selective DNA binding anti-tumor agent, Hedamycin[J]. J Boil Chem,2005; 280(10):116-122.
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[8] LI F,ACKERMANNE J,BENI C F,et a1.Pleiotropic cell-division defects and apoptosis induced by inteference with survivin function[J].Nat Cel Biol,1999,1(8):461-466.
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[10] Vicente A,Torres JC,Tapia DA,et a1.E-Cadherin Is Required for Caveolin-1-Mediated Down-Regulation of the Inhibitor of Apoptosis Protein Survivin via Reduced β-Catenin-Tcf/Lef-Dependent Transcription. Mol Cell Biol,2007; 27(21): 7703–7717.
[11] Vicente A, Torres JC, Tapia DA, et a1. Caveolin-1 controls cell proliferation and cell death by suppressing expression of the inhibitor of apoptosis protein surviving. Journal of Cell Science, 2006;119(11), 1812-1823 .
[12] Olie RA,SimoesWust AP, et al.A novel antisense oligonucleotide targeting surviving expression induces apoptosis and sensitizes lung cancer cells to chemotherapy.Cancer Res.1998;60:2805-2809.
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[15] Wall NR,O'Connor DS,Plescia J,Pommier Y,Altieri DC.Suppression of surviving phosphorylation on Thr34 by flavopiridol enhances tumor cell apoptosis.Cancer Res.2003;63(1):230-235.
[1] Song E, Lee SK, Wang J, Ince N, et al. RNA interference targeting Fas protects mice from fulminant hepatitis. Nat Med, 2003;9(3):347-351.
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[1] Hammond SM, Boettcher S, Caudy AA,et a1.Argonaute2, a link between genetic and biochemical analyses of RNAi. Science, 2001; 293(5532):1146-1150.
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[6] Cheng JC, Moore TB, Sakamoto KM.RNA interference and human disease. Mol Genet Metab, 2003; 80:121-128.
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[1] Devereaux QL,Takahashi R,Salvesen GS,et al.X-linked IAPs is a direct inhibitor of cell death proteases[J].Nature,1997;388(6639):300-304.
[2] Swana HS,Grossman D,Anthony JN,et al.Tumor content of the antiapoptosis molecule surviving and recurrence of bladder cancer [J].N Engl J Med,1999;341(6):452-453.
[3] Shariat SF,Casella R,Khoddami SM,et al.Urine detection of survivin is a sensitive marker for the noninvasive diagnosis of bladder cancer [J].J Urol,2004;171(2):626-630.
[4] Albini A,Iwamoto Y,Kleinman HK,et al.A rapid in vitro assay for quantitating the invasive potential of tumor cells.Cancer Res,1987;47(12):3239-3245.
[5] Mallo GV,Soubeyran P. Expression of Cdx1 and Cdx2 homeotic genes to leads to reduced malignancy in colon cancer derived cells.J Bio Chem,1998,273(22):1430-1436.
[6] 韩锐, 主编.抗癌药物研究与实验技术.北京:北京医科大学、协和医科大学联合出版社,1997,353-354.
[7] 曹贵华,吴小候,张尧,等. 膀胱癌患者尿脱落细胞存活素表达的临床意义. 中华泌尿外科杂志,2004;25(6):377-379.
[8] Kleiman H,McGarvey M,Hassell J,et al. Basement membrane complexes with biological activity.Biochemistry,1986,25(2):312-318.
[9] Repesh LA.A new in vitro assay for quantitation tumor cell invasion. Invasion Metast,1989; 9(3):192-208.
[10] Grimstad IA.Direct evidence that cancer cell locomotion contributes importantly to invasion. Exp Cell Res, 1987;173(2):515-523.
[11] Vicente A,Torres JC,Tapia DA et a1.E-Cadherin Is Required for Caveolin-1-Mediated Down-Regulation of the Inhibitor of Apoptosis Protein Survivin via Reduced β-Catenin-Tcf/Lef-Dependent Transcription. Mol Cell Biol,2007;27(21): 7703–7717.
[12] Vicente A, Torres JC, Tapia DA, et a1. Caveolin-1 controls cell proliferation and cell death by suppressing expression of the inhibitor of apoptosis protein surviving. Journal of Cell Science, 2006;119(11), 1812-1823 .
[1] Nasu S, Yagihashi A,Izawa, et al.Survivin mRNA expression in patients with breast cancer. Anticancer Res 2002; 22:1839-1842.12
[2] Vleminckx K,Vakaet L,Mareel M,et al.Genetic manipulation of E-cadherin expression by epithelial tumour cells reveals an invasion suppressor role.Cell,1991;66(1):10-109.13
[3] Gammallo C,Palacios J,Moreno G,et al.Beta-catenin expression pattern in stage Ⅰa ndⅡ ovarian cancinomas:relationship with beta-catenin gene mutations.Clinicopathological feature,and clinical outcome.Am J Pathol,1999,155(2):527-536.14
[4] Cui J,Zhou XD,Liu YK,et al.Mutation and overexpression of the beta-catenin gene may play an important role in primary hepatocellular carcinoma among Chinese people.J Cancer Res Clin Oncol,2001;127(9):577-581. 15
[5] 郑清友,靳风烁.凋亡抑制因子 survivin 在膀胱移行细胞癌中的表达及意义[J]. 第三军医大学学报 2005;27(l0):1030-1032.16
[6] Fukuda S, Pelus LM.Regulation of the inhibitor-of-apoptosis family member Survivin in normal cord blood and bone marrow CD34 cells by hematopoietic growth factor:implication of Survivin expression in normal hematopoiesis.Blood, 2001;98:2091-2100. 17
[7] Seliger B,Cabrera T,Garrido F,et al.HLA class I antigen abnormalities and immune escape by malignant cells.Semin Cancer Biol,2002;12:3-13.18
[8] Kren L,Brazdil J,Hermanova M,et al.Prognostic significance of anti-apoptosis proteins surviving and bcl-2 in non-small cell lung carcinomas:a clinical pathologic study of 102 cases. Appl Immunohistochem Mol Morphol, 2004;12(1):44-49.
[9] Cao C,Mu Y,Hallahan DE,et al.XIAP and surviving as therapeutic targets for radiation sensitization in preclinical models of lung cancer .Oncogen,2004;23(42):7047-7052.
[10] Blanc OP,Yu J,Simosa H,et al.Inhibitor of apoptosis protein Survivin regulates vascular injury.Nat Med,2002;8:987-994.
[11] Krysan K,Dalwadi H,Sharma S,et al.Cyclooxygenase 2-dependent expression of surviving is critical for apoptosis resistance in non-small cell lung cancer.Cancer Res,2004;64(18):6359-6362.
[1] Ambrosini G, AItieri DC, et al. A nevel anti-apoptosisgene, Survivn, expressed in cancer and lymphoma[J]. Nature MED,1997;3:917-921.
[2] Badran A, yoshida A, Ishikawa K, et al, Identification of anovel splice variant of the human anti-apoptopsis gene surviving[J]. Biochem Biophys Res Commum,2004;314(3):902.
[3] Uren A G, Wang l. Pakusch M, et al. Survivin and the inner centromere protein INCENP show similar cell-cycle localization and gene knockout phenotype[J]. Curr Biol,2002;10(21):1319.
[4] Deveraux QL, Reed JC. IAP family proteins- suppressors of apoptosis[J].Genes, 1999; 13 (3): 239 -252.
[5] Suzuki A, Hayashida M, Ito T, et al, Survivin initiates cell cycle entry by the complex activation with CDK4 /p16(INK4a)and CDK2, cyclinE complex activation[J]. Oncogene. 2000; 19(29): 3225-3234.
[6] Suzuki A, Ito T, Kawano H, et al, Suevivin initiates procaspase/P21 complex formation as a result of interaction with CDK4 to resist FAS-mediated cell death[J].Oncogene,2000; 19(10):1346-1353.
[7] Wheatley SP, Kandels L, Adams RR, et al. INCENP binds directly to tubulin, and requires dynamic microtubules to target to the cleavage furrow[J]. Exp, Cell Res,2001b;262:122-127.
[8] Oconnor DS, Schechner JS, Adida C, et al. Angioptosis during angiogenesis by surviving express in endothelial cell[J].Am J Pathol,2000;156(6):393.
[9] Papapetropoulos A, Fulton D, Mubboubi K, et al. Angiopioetin-1 inhibits endothelial cell[J]. J Biol Chem, 2000;275(13):9102.
[10] Alticri DC. Validating surviving as a cancer therapeutic target[J]. Nat.Rev. Cancer,2003;3:46-54.
[11] O'Connor D S, Schechner J S, Adida C. Control of apoptosis during angiogenesis by Survivin expression in endothelial cells[J].Am J Pathol,2000; 156(2): 393-398.
[12] Lu CD, Altieri DC. Tanigawa N. Expression of a novel anti-apoptosis gene, Survivin, correlated with tumor cell apoptosis and P53 accumulation in gastric carcinomas[J]. Cancer Res,1998;58(9):1808.
[13] Endoh A, Asanuma K, Moriai R, et al. Expression of surviving mRNA in CD34-positive cells[J]. Clin Chim AcTa,2001;306:149-151.
[14] Kawasaki H, Altieri DC, LuCD, et al. Unhibition of apoptosis by Survivin predicts Shorter Survivin rates in colorectal cancer[J].Cancer Res,1998;56(22):5071.
[15] Swana HS, Grossman D, Anthony JN, et al. Tumor content of the anti-apoplosis molecule Survivin and recurrence of bladder cancer[J]. N Engl J MED,1999;341:452-453.
[16] ZHANG Xiang-yang, ZENG Qiang, QI Fan,et al. Expression of Survivin protein in prostate cancer and its clinical sign ificance[J]. China Journl Of Modern Medicine, 2006;16:1060-1062.
[17] Mono M, Rosell R, Felip E, et al. A novel anti-apoptosis gene Rexpression of Survivin messenger RNA as a prognosis marker in nonsmall-cell lung cancers[J]. J Clin Oncol. 1999; 17: 2100-2104.
[18] Hou Yan, Hu Qun, Liu Aiguo, Zhang Liuqing, et al. Expression of survivin and its location in cell and clinical significance in pediatric acute leukemia[J]. Journal Of China PediaTric Blood And Cancer, 2006; 1:6-8.
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