期刊文献+

Effect of antisense human telomerase RNA on malignant behaviors of gastric carcinoma cell line SGC-7901

Effect of antisense human telomerase RNA on malignant behaviors of gastric carcinoma cell line SGC-7901
下载PDF
导出
摘要 Objective:To studytheeffectsof antisensehumantelomeraseRNA(ahTR)transfectionon themalignantbeha-viorsof gastriccarcinomacelllineSGC-7901anditspotentialroleingenetherapyfortumor.Methods:AnantisensehTR eukaryoticexpressionvectorcontainingthesequenceof templateregionof telomererepeatswas transfectedintogastric carcinomacelllineSGC-7901withliposomeDOTAP.Theexpressionsof hTRRNAandantisensehTRRNAwereob-servedwithRT-PCR,telomeraseactivitywithPCR-ELISA.Telomerelengthwas measuredwithSouthernblot.Cellmor-phologyandcellularproliferationcapacitywerestudiedwithMTTassay.Cellcycledistributionandapoptoticstatewere observedwithflowcytometry.Efficiencyof cloneformationin softagarandtumorigencityin nudemicewereexamined andevaluatedinahTR-transfected7901cells,andplasmidpCL-neotransfected7901cellsandparental7901cellsserved as control.Results:AnantisensehTReukaryoticexpressionvectorwastransfectedinto7901cellssuccessfully.Thetelom-eraseactivityin ahTR-transfected7901cellswas decreasedfrom100%to about25%,andtelomerelengthin thecells shortenedfrom4.08kb to3.35kb at60populationdoublings(PDs).Comparedwithparental7901andpCL-neotransfect-ed7901cells,ahTR-transfected7901cellsdisplayedsomemorphologicalchanges,includingdecreasedcellatypiaandnu-cleus/cytoplasmratiounderlightmicroscope.Furthermore,ahTR-transfected7901cellsdisplayedgrowthinhibition,de-creasedinvasivecapacityin Borden’schamberinvasivemodel,increasedG 0 /G 1 phaserateandapoptoticrate,andrestored contactinhibitionanddensityinhibition.Surprisingly,ahTR-transfected7901cellslosttheircapacityof cloneformationin softagarandcarcinogensisinnudemice.Conclusion:AntisensehTRtransfectioncaninduce7901celldifferentiationand reverseitsmalignantphenotype.Thisstudyprovidesan excitingapproachfor cancertherapythroughtheinhibitionof telomeraseactivitywithantisensegeneandothertelomeraseinhibitors. Objective:To studytheeffectsof antisensehumantelomeraseRNA(ahTR)transfectionon themalignantbeha-viorsof gastriccarcinomacelllineSGC-7901anditspotentialroleingenetherapyfortumor.Methods:AnantisensehTR eukaryoticexpressionvectorcontainingthesequenceof templateregionof telomererepeatswas transfectedintogastric carcinomacelllineSGC-7901withliposomeDOTAP.Theexpressionsof hTRRNAandantisensehTRRNAwereob-servedwithRT-PCR,telomeraseactivitywithPCR-ELISA.Telomerelengthwas measuredwithSouthernblot.Cellmor-phologyandcellularproliferationcapacitywerestudiedwithMTTassay.Cellcycledistributionandapoptoticstatewere observedwithflowcytometry.Efficiencyof cloneformationin softagarandtumorigencityin nudemicewereexamined andevaluatedinahTR-transfected7901cells,andplasmidpCL-neotransfected7901cellsandparental7901cellsserved as control.Results:AnantisensehTReukaryoticexpressionvectorwastransfectedinto7901cellssuccessfully.Thetelom-eraseactivityin ahTR-transfected7901cellswas decreasedfrom100%to about25%,andtelomerelengthin thecells shortenedfrom4.08kb to3.35kb at60populationdoublings(PDs).Comparedwithparental7901andpCL-neotransfect-ed7901cells,ahTR-transfected7901cellsdisplayedsomemorphologicalchanges,includingdecreasedcellatypiaandnu-cleus/cytoplasmratiounderlightmicroscope.Furthermore,ahTR-transfected7901cellsdisplayedgrowthinhibition,de-creasedinvasivecapacityin Borden'schamberinvasivemodel,increasedG 0 /G 1 phaserateandapoptoticrate,andrestored contactinhibitionanddensityinhibition.Surprisingly,ahTR-transfected7901cellslosttheircapacityof cloneformationin softagarandcarcinogensisinnudemice.Conclusion:AntisensehTRtransfectioncaninduce7901celldifferentiationand reverseitsmalignantphenotype.Thisstudyprovidesan excitingapproachfor cancertherapythroughtheinhibitionof telomeraseactivitywithantisensegeneandothertelomeraseinhibitors.
出处 《Journal of Medical Colleges of PLA(China)》 CAS 2001年第4期255-259,共5页 中国人民解放军军医大学学报(英文版)
基金 SupportedbyNationalNaturalScienceFundationofChina(No.39770302)
关键词 human TELOMERASE RNA components ANTISENSE GENE TELOMERASE EUKARYOTIC expression vector GENE therapy gastric carcinoma cell line humantelomeraseRNAcomponents antisensegene telomerase eukaryoticexpressionvector genetherapy gastriccarcinomacellline
  • 相关文献

参考文献20

  • 1[1]Morin GB. The human telomere terminal transterase enzyme is a ribonucleoprotein that synthesize TTAGGG repeats. Cell, 1989; 59(3): 521
  • 2[2]Kim NW, Piatyszek MA, Prowse KR et al. Specific association of human telomerase activity with immortal cells and cancer. Science, 1994; 266(5193):2011
  • 3[3]Harley CB, Futcher AB, Greider CW. Telomeres shorter during aging of human fibroblasts. Nature, 1990; 345 (6274): 458
  • 4[4]Feng J, Funk WD, Wang SS et al. The RNA component of human telomerase.Science, 1995; 269(5228): 1236
  • 5[6]Counter CM, Avillion AA, LeFeure CE et al. Telomerase shortening association with chromosome instability is arrested in immortal cells which express telomerase activity. EMBO J, 1992; 11(5): 1921
  • 6杨仕明,房殿春,罗元辉,鲁荣,刘为纹.胃癌及癌前组织中端粒酶活性的检测及其临床意义[J].中华医学杂志,1998,78(3):207-209. 被引量:52
  • 7[8]Hiyama E, Yokoyama T, Tatsumoto N et al. Telomerase activity in gastric cancer. Cancer Res, 1995;55(15): 3258
  • 8[9]Tahara H, Kuniyasu H, Yokozaki H et al. Telomerase activity in preneoplastic and neoplastic gastric and colorectal lesions. Clin Cancer Res, 1995;11(7): 1245
  • 9[10]Kuniyasu H, Domen T, Hamamoto T et al. Expression of human telomerase RNA is an early event of stomach carcinogensis. Jpn J Cancer Res, 1997; 88(2): 103
  • 10[11]Mata JE, Joshi SS, Palen B et al. A hexameric phosphorothioate oligonucleotide telomerase inhibitor arrests growth of Burkitt's lymphoma cells in vitro and in vivo. Toxicol Appl Pharmacol, 1997; 144(1): 189

二级参考文献2

  • 1杨仕明,中华消化内镜杂志,1997年,19卷,401页
  • 2Feng J L,Science,1995年,269卷,1326页

共引文献51

相关作者

内容加载中请稍等...

相关机构

内容加载中请稍等...

相关主题

内容加载中请稍等...

浏览历史

内容加载中请稍等...
;
使用帮助 返回顶部