GKLF基因对人胃癌细胞株SGC-7901生物学行为影响的实验研究
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摘要
第一部分GKLF、IKLF在胃癌组织和胃癌细胞株中的表达及意义
目的:研究胃癌组织和胃癌细胞株中GKLF、IKLF的表达及临床意义。方法:采用荧光实时定量PCR法检测胃癌组织和胃癌细胞株中GKLF mRNA、IKLF mRNA的表达,免疫组织化学法(IHC)检测胃癌组织及其远端正常胃组织中GKLF、IKLF蛋白的表达,Western blot和免疫细胞化学法(ICC)检测人正常胃上皮细胞株GES-1及胃癌细胞株MKN-28、SGC-7901、BGC-823、HGC-27中GKLF、IKLF蛋白的表达。结果:胃癌组织中GKLF mRNA的相对表达量明显低于远端正常胃组织、IKLF mRNA的相对表达量明显高于远端正常胃组织(P <0.05)、胃癌组织中GKLF mRNA、IKLF mRNA的表达水平与组织分化程度无关,GKLF蛋白总阳性率显著低于远端正常胃组织、IKLF蛋白总阳性率显著高于远端正常胃组织(P <0.05),GKLF、IKLF蛋白表达与胃癌患者的年龄、性别、分化程度、Lauren分型无关,与淋巴结是否有转移及pTNM分期有关(P <0.05);胃癌细胞株中GKLF mRNA和蛋白的相对表达量低于人正常胃上皮细胞株GES-1、IKLF mRNA和蛋白的相对表达量则高于细胞株GES-1(P <0.05)。结论:胃癌组织和胃癌细胞株中存在GKLF低表达、IKLF高表达,GKLF、IKLF在胃癌发生、发展中起一定的作用,检测GKLF、IKLF的表达有助于判断胃癌患者病情程度和预后。
第二部分重组质粒pcDNA3.1-GKLF的转染及稳定细胞株的建立
目的:建立高表达GKLF的稳定转染细胞株,以进一步观察其对人胃癌细胞株SGC-7901生物学行为的影响。方法:用脂质体转染法将重组质粒pcDNA3.1-GKLF转染人胃癌细胞株SGC-7901,通过G418筛选,建立稳定转染的SGC7901-pcDNA3.1-GKLF细胞株,用荧光实时定量PCR法、Western blot和ICC法检测GKLF mRNA和蛋白的表达。结果:建立了稳定转染的SGC7901-pcDNA3.1-GKLF细胞株,成功地表达目的基因。结论:成功建立稳定转染的SGC7901-pcDNA3.1-GKLF细胞株,为下一步探讨GKLF基因对胃癌生物学行为影响的体内外实验研究奠定基础。
第三部分GKLF基因转染对人胃癌细胞株SGC-7901生物学行为影响的体外实验研究
目的:体外观察外源性GKLF基因转染对人胃癌细胞株SGC-7901增殖活性和侵袭力的影响,探讨GKLF在胃癌中的作用机制。方法:应用MTT法(四甲基偶氮唑蓝比色法)、流式细胞仪、克隆形成实验和体外细胞侵袭实验分别研究GKLF基因转染前、后人胃癌细胞株SGC-7901增殖和侵袭活性的变化。RT-PCR法、Western blot法分别检测GKLF基因转染前、后人胃癌细胞株SGC-7901中细胞周期蛋白D1(Cyclin D1)、Ki-67、E-钙粘附分子(E-cadherin) mRNA和蛋白的表达。结果:与SGC-7901组和SGC7901-pcDNA3.1组相比,SGC7901-pcDNA3.1-GKLF组细胞生长速度减慢、细胞出现G0/G1期部分阻滞、克隆形成率低、细胞侵袭力明显减弱(P < 0.05)。SGC7901-pcDNA3.1-GKLF组细胞Cyclin D1、Ki-67、E-cadherin mRNA和蛋白的表达水平均低于SGC-7901组和SGC7901-pcDNA3.1组(P <0.05)。结论:GKLF基因可能通过下调Cyclin D1、Ki-67、E-cadherin的表达,而使人胃癌细胞株SGC-7901的增殖活性和侵袭力降低。
第四部分GKLF基因转染对人胃癌细胞株SGC-7901生物学行为影响的体内实验研究
目的:体内观察外源性GKLF基因转染对人胃癌裸鼠皮下移植瘤生长、转移的影响,并探讨GKLF在胃癌中的作用机制,从而为胃癌的基因治疗提供新的思路。方法:选用36只BALB/C-nu/nu裸鼠进行体内实验,分两批进行。每批裸鼠18只,各随机分为三组,每组分别注射等量的SGC7901-pcDNA3.1-GKLF、SGC7901-pcDNA3.1和SGC-7901细胞(2×107个/200μl/只)。第一批,将细胞注射于每只裸鼠右胁腹前肢皮下,接种6周后处死裸鼠,观察肿瘤生长状况、成瘤潜伏期,IHC法检测裸鼠皮下移植瘤组织内GKLF、Ki-67、E-cadherin、VEGF蛋白表达情况,测定皮下移植瘤组织中MVD值;同时用B超观察皮下移植瘤大小、血流信号及腹腔内转移情况。第二批,将细胞经尾静脉接种于裸鼠,接种6周后处死裸鼠,显微镜下观察有无肺转移。结果:与SGC-7901组和SGC7901-pcDNA3.1组相比,SGC7901-pcDNA3.1-GKLF组成瘤潜伏期延长、皮下移植瘤体积和瘤重较小(P <0.05),皮下移植瘤组织内GKLF蛋白表达升高、Ki-67、E-cadherin、VEGF蛋白表达均降低,微血管密度(MVD)值降低。B超显示:SGC7901-pcDNA3.1-GKLF组皮下移植瘤较小,血流信号I级。所有裸鼠均未见肺、腹腔转移。结论:GKLF基因可能通过下调Ki-67、E-cadherin、VEGF的表达,从而抑制肿瘤的生长,减少肿瘤中新生血管的生成,以GKLF为靶点的基因治疗有潜在的临床应用前景。
Part 1 Expression and clinical significance of GKLF and IKLF in human gastric carcinoma tissues and cell lines
Objective: To study the expression and clinical significance of GKLF and IKLF in human gastric carcinoma tissues and cell lines.Methods: Expressions of GKLF mRNA and IKLF mRNA in gastric carcinoma tissues and cell lines were detected by real-time fluorescence quantitative PCR.Expressions of GKLF protein and IKLF protein in gastric carcinoma tissues and adjacent normal gastric tissues were detected by immunohistochemistry(IHC) .Expressions of GKLF protein and IKLF protein in human normal gastric epithelium cell line (GES-1) and gastric carcinoma cell lines (MKN-28、SGC-7901、BGC-823、HGC-27)were detected respectively by Western blot and immunocytochemistry(ICC).Results: The expression level of GKLF mRNA in gastric carcinoma tissues was significantly lower than that in adjacent normal gastric tissues, the expression level of IKLF mRNA in gastric carcinoma tissues was significantly higher than that in adjacent normal gastric tissues(P <0.05).The levels of GKLF mRNA and IKLF mRNA in gastric carcinoma tissues were uncorrelated with differentiation.Positive expression rate of GKLF protein in the carcinoma tissues was significantly lower than that in adjacent normal gastric tissues .Positive expression rate of IKLF protein in the carcinoma tissues was significantly higher than that in adjacent normal gastric tissues(P <0.05).The expressions of GKLF protein and IKLF protein were uncorrelated with age,gender,differentiation and Lauren’s classification.They were correlated with lymph node involvement and clinical stage(P <0.05).The levels of GKLF mRNA and GKLF protein in four gastric carcinoma cell lines were lower than that in human normal gastric epithelium cell line (GES-1) . The IKLF mRNA and IKLF protein levels in four gastric carcinoma cell lines were higher than that in GES-1(P <0.05).Conclusion:The low expression of GKLF and high expression of IKLF were existed both in gastric carcinoma tissues and cell lines, GKLF and IKLF play roles in the carcinogenesis and progression of gastric carcinoma in a way.To examine the expression of GKLF and IKLF may be useful in judging the degree and prognosis of human gastric carcinoma.
Part 2 The transfection of recombinant plasmid pcDNA3.1-GKLF and the establishment of stable transfected cell line
Objective:To establish stable transfected SGC7901-pcDNA3.1-GKLF cell line which expressed high level of GKLF.To observe the impact of biological behaviors of GKLF gene on human gastric carcinoma cell line SGC-7901.Methods: The recombinant plasmid of pcDNA3.1-GKLF was transfected into SGC-7901 cell by lipofectin-mediated method.After screening culture by G418,stable transfected SGC7901-pcDNA3.1-GKLF cell line was established,and the levels of GKLF mRNA and GKLF protein were identified by real-time fluorescence quantitative PCR、Western blot and immunocytochemistry(ICC).Results: The stable transfected SGC7901-pcDNA3.1-GKLF cell line was established.The GKLF gene was expressed successfully in the cell line.Conclusion: The establishment of stable transfected SGC7901-pcDNA3.1-GKLF cell line provide solid foundation for further experimental studies in vitro and in vivo of the impact of biological behaviors of GKLF gene on human gastric carcinoma.
Part 3 Experimental study of the impact of biological behaviors on human gastric carcinoma cell line SGC-7901 by GKLF gene transfection in vitro
Objective:To observe the effects of GKLF gene transfection on proliferation and invasion of human gastric carcinoma cell line SGC-7901 in vitro,to study the mechanism GKLF gene in human gastric carcinoma.Methods: Proliferation and invasion ability were measured before and after transfection by MTT assay、flow cytometry、colony formation assay and cell invasion assay. The mRNA and protein levels of Cyclin D1、Ki-67、E-cadherin were detected respectively by reverse transcription-polymerase chain reaction(RT-PCR) and Western blot . Results: The proliferative speed of SGC7901-pcDNA3.1-GKLF group was markedly slower than that of SGC-7901 and SGC7901-pcDNA3.1 groups(P <0.05).GKLF gene transfection caused part of the G0/G1 arrest,decreased clone formation rate and the invasion ability(P <0.05).The mRNA and protein levels of Cyclin D1、Ki-67、E-cadherin of SGC7901-pcDNA3.1-GKLF group were lower than that of SGC-7901 and SGC7901-pcDNA3.1 groups ( P <0.05).Conclusion: Transfection with GKLF gene might suppress proliferation and invasion ability of human gastric carcinoma cell line SGC-7901 by downregulation the expressions of Cyclin D1、Ki-67、E-cadherin.
Part 4 Experimental study of the impact of biological behaviors on human gastric carcinoma cell line SGC-7901 by GKLF gene transfection in vivo
Objective:To observe the effects of GKLF gene transfection on growth and metastasis of human gastric carcinoma cell line SGC-7901 xenograft in nude mice,to explore the potential mechanism of GKLF gene in gastric carcinoma and to bring a new method of gene therapy for human gastric carcinoma.Methods: We carried out an in vivo study with 36 BALB/C-nu/nu nude mice which divided into two parts.Every 18 nude mice were randomly divided into 3 groups.SGC7901-pcDNA3.1-GKLF、SGC7901-pcDNA3.1、SGC-7901 were injected into 3 groups nude mice .Every group nude mice injected with the same cell and volume(2×107 cells/200μl/mouse) .In part one, cells were injected into right costal abdomen subcutis of nude mice.The mice were killed 6 weeks later after injection and the changes of weight、volume、latency、state were observed. The expressions of GKLF、Ki-67、E-cadherin、VEGF and CD34 in xenograft tissues were stained by immunohistochemistry(IHC).The microvessel density (MVD) of xenograft tissues were evaluated.The size of tumour、blood stream signal and abdominal cavity were examined for tumour metastasis by ultrasonic.In part two,cells were injected into the tail vein of nude mice.The mice were killed 6 weeks later after injection and lung were examined for tumour metastasis by microscope. Results:Compared with SGC7901-pcDNA3.1、SGC-7901 groups,for SGC7901-pcDNA3.1-GKLF group,the stage of latency lengthened and growth of xenograft were inhibited,and the volume and weight of xenograft tissues were small(P <0.05).GKLF protein of xenograft tissues in SGC7901-pcDNA3.1-GKLF group increased.The expressions of Ki-67、E-cadherin、VEGF and MVD value decreased.The size of xenograft tissues were small, blood stream signal were in stage I.No metastasis sites of lung and abdominal cavity were seen in all nude mice.Conclusion: GKLF gene might inhibit the growth of tumour and reduce the formation of new blood vessel by downregulating the expressions of Ki-67、E-cadherin、VEGF.So GKLF gene has potential application value in clinical of being target of gene therapy.
目的:研究胃癌组织和胃癌细胞株中GKLF、IKLF的表达及临床意义。方法:采用荧光实时定量PCR法检测胃癌组织和胃癌细胞株中GKLF mRNA、IKLF mRNA的表达,免疫组织化学法(IHC)检测胃癌组织及其远端正常胃组织中GKLF、IKLF蛋白的表达,Western blot和免疫细胞化学法(ICC)检测人正常胃上皮细胞株GES-1及胃癌细胞株MKN-28、SGC-7901、BGC-823、HGC-27中GKLF、IKLF蛋白的表达。结果:胃癌组织中GKLF mRNA的相对表达量明显低于远端正常胃组织、IKLF mRNA的相对表达量明显高于远端正常胃组织(P <0.05)、胃癌组织中GKLF mRNA、IKLF mRNA的表达水平与组织分化程度无关,GKLF蛋白总阳性率显著低于远端正常胃组织、IKLF蛋白总阳性率显著高于远端正常胃组织(P <0.05),GKLF、IKLF蛋白表达与胃癌患者的年龄、性别、分化程度、Lauren分型无关,与淋巴结是否有转移及pTNM分期有关(P <0.05);胃癌细胞株中GKLF mRNA和蛋白的相对表达量低于人正常胃上皮细胞株GES-1、IKLF mRNA和蛋白的相对表达量则高于细胞株GES-1(P <0.05)。结论:胃癌组织和胃癌细胞株中存在GKLF低表达、IKLF高表达,GKLF、IKLF在胃癌发生、发展中起一定的作用,检测GKLF、IKLF的表达有助于判断胃癌患者病情程度和预后。
第二部分重组质粒pcDNA3.1-GKLF的转染及稳定细胞株的建立
目的:建立高表达GKLF的稳定转染细胞株,以进一步观察其对人胃癌细胞株SGC-7901生物学行为的影响。方法:用脂质体转染法将重组质粒pcDNA3.1-GKLF转染人胃癌细胞株SGC-7901,通过G418筛选,建立稳定转染的SGC7901-pcDNA3.1-GKLF细胞株,用荧光实时定量PCR法、Western blot和ICC法检测GKLF mRNA和蛋白的表达。结果:建立了稳定转染的SGC7901-pcDNA3.1-GKLF细胞株,成功地表达目的基因。结论:成功建立稳定转染的SGC7901-pcDNA3.1-GKLF细胞株,为下一步探讨GKLF基因对胃癌生物学行为影响的体内外实验研究奠定基础。
第三部分GKLF基因转染对人胃癌细胞株SGC-7901生物学行为影响的体外实验研究
目的:体外观察外源性GKLF基因转染对人胃癌细胞株SGC-7901增殖活性和侵袭力的影响,探讨GKLF在胃癌中的作用机制。方法:应用MTT法(四甲基偶氮唑蓝比色法)、流式细胞仪、克隆形成实验和体外细胞侵袭实验分别研究GKLF基因转染前、后人胃癌细胞株SGC-7901增殖和侵袭活性的变化。RT-PCR法、Western blot法分别检测GKLF基因转染前、后人胃癌细胞株SGC-7901中细胞周期蛋白D1(Cyclin D1)、Ki-67、E-钙粘附分子(E-cadherin) mRNA和蛋白的表达。结果:与SGC-7901组和SGC7901-pcDNA3.1组相比,SGC7901-pcDNA3.1-GKLF组细胞生长速度减慢、细胞出现G0/G1期部分阻滞、克隆形成率低、细胞侵袭力明显减弱(P < 0.05)。SGC7901-pcDNA3.1-GKLF组细胞Cyclin D1、Ki-67、E-cadherin mRNA和蛋白的表达水平均低于SGC-7901组和SGC7901-pcDNA3.1组(P <0.05)。结论:GKLF基因可能通过下调Cyclin D1、Ki-67、E-cadherin的表达,而使人胃癌细胞株SGC-7901的增殖活性和侵袭力降低。
第四部分GKLF基因转染对人胃癌细胞株SGC-7901生物学行为影响的体内实验研究
目的:体内观察外源性GKLF基因转染对人胃癌裸鼠皮下移植瘤生长、转移的影响,并探讨GKLF在胃癌中的作用机制,从而为胃癌的基因治疗提供新的思路。方法:选用36只BALB/C-nu/nu裸鼠进行体内实验,分两批进行。每批裸鼠18只,各随机分为三组,每组分别注射等量的SGC7901-pcDNA3.1-GKLF、SGC7901-pcDNA3.1和SGC-7901细胞(2×107个/200μl/只)。第一批,将细胞注射于每只裸鼠右胁腹前肢皮下,接种6周后处死裸鼠,观察肿瘤生长状况、成瘤潜伏期,IHC法检测裸鼠皮下移植瘤组织内GKLF、Ki-67、E-cadherin、VEGF蛋白表达情况,测定皮下移植瘤组织中MVD值;同时用B超观察皮下移植瘤大小、血流信号及腹腔内转移情况。第二批,将细胞经尾静脉接种于裸鼠,接种6周后处死裸鼠,显微镜下观察有无肺转移。结果:与SGC-7901组和SGC7901-pcDNA3.1组相比,SGC7901-pcDNA3.1-GKLF组成瘤潜伏期延长、皮下移植瘤体积和瘤重较小(P <0.05),皮下移植瘤组织内GKLF蛋白表达升高、Ki-67、E-cadherin、VEGF蛋白表达均降低,微血管密度(MVD)值降低。B超显示:SGC7901-pcDNA3.1-GKLF组皮下移植瘤较小,血流信号I级。所有裸鼠均未见肺、腹腔转移。结论:GKLF基因可能通过下调Ki-67、E-cadherin、VEGF的表达,从而抑制肿瘤的生长,减少肿瘤中新生血管的生成,以GKLF为靶点的基因治疗有潜在的临床应用前景。
Part 1 Expression and clinical significance of GKLF and IKLF in human gastric carcinoma tissues and cell lines
Objective: To study the expression and clinical significance of GKLF and IKLF in human gastric carcinoma tissues and cell lines.Methods: Expressions of GKLF mRNA and IKLF mRNA in gastric carcinoma tissues and cell lines were detected by real-time fluorescence quantitative PCR.Expressions of GKLF protein and IKLF protein in gastric carcinoma tissues and adjacent normal gastric tissues were detected by immunohistochemistry(IHC) .Expressions of GKLF protein and IKLF protein in human normal gastric epithelium cell line (GES-1) and gastric carcinoma cell lines (MKN-28、SGC-7901、BGC-823、HGC-27)were detected respectively by Western blot and immunocytochemistry(ICC).Results: The expression level of GKLF mRNA in gastric carcinoma tissues was significantly lower than that in adjacent normal gastric tissues, the expression level of IKLF mRNA in gastric carcinoma tissues was significantly higher than that in adjacent normal gastric tissues(P <0.05).The levels of GKLF mRNA and IKLF mRNA in gastric carcinoma tissues were uncorrelated with differentiation.Positive expression rate of GKLF protein in the carcinoma tissues was significantly lower than that in adjacent normal gastric tissues .Positive expression rate of IKLF protein in the carcinoma tissues was significantly higher than that in adjacent normal gastric tissues(P <0.05).The expressions of GKLF protein and IKLF protein were uncorrelated with age,gender,differentiation and Lauren’s classification.They were correlated with lymph node involvement and clinical stage(P <0.05).The levels of GKLF mRNA and GKLF protein in four gastric carcinoma cell lines were lower than that in human normal gastric epithelium cell line (GES-1) . The IKLF mRNA and IKLF protein levels in four gastric carcinoma cell lines were higher than that in GES-1(P <0.05).Conclusion:The low expression of GKLF and high expression of IKLF were existed both in gastric carcinoma tissues and cell lines, GKLF and IKLF play roles in the carcinogenesis and progression of gastric carcinoma in a way.To examine the expression of GKLF and IKLF may be useful in judging the degree and prognosis of human gastric carcinoma.
Part 2 The transfection of recombinant plasmid pcDNA3.1-GKLF and the establishment of stable transfected cell line
Objective:To establish stable transfected SGC7901-pcDNA3.1-GKLF cell line which expressed high level of GKLF.To observe the impact of biological behaviors of GKLF gene on human gastric carcinoma cell line SGC-7901.Methods: The recombinant plasmid of pcDNA3.1-GKLF was transfected into SGC-7901 cell by lipofectin-mediated method.After screening culture by G418,stable transfected SGC7901-pcDNA3.1-GKLF cell line was established,and the levels of GKLF mRNA and GKLF protein were identified by real-time fluorescence quantitative PCR、Western blot and immunocytochemistry(ICC).Results: The stable transfected SGC7901-pcDNA3.1-GKLF cell line was established.The GKLF gene was expressed successfully in the cell line.Conclusion: The establishment of stable transfected SGC7901-pcDNA3.1-GKLF cell line provide solid foundation for further experimental studies in vitro and in vivo of the impact of biological behaviors of GKLF gene on human gastric carcinoma.
Part 3 Experimental study of the impact of biological behaviors on human gastric carcinoma cell line SGC-7901 by GKLF gene transfection in vitro
Objective:To observe the effects of GKLF gene transfection on proliferation and invasion of human gastric carcinoma cell line SGC-7901 in vitro,to study the mechanism GKLF gene in human gastric carcinoma.Methods: Proliferation and invasion ability were measured before and after transfection by MTT assay、flow cytometry、colony formation assay and cell invasion assay. The mRNA and protein levels of Cyclin D1、Ki-67、E-cadherin were detected respectively by reverse transcription-polymerase chain reaction(RT-PCR) and Western blot . Results: The proliferative speed of SGC7901-pcDNA3.1-GKLF group was markedly slower than that of SGC-7901 and SGC7901-pcDNA3.1 groups(P <0.05).GKLF gene transfection caused part of the G0/G1 arrest,decreased clone formation rate and the invasion ability(P <0.05).The mRNA and protein levels of Cyclin D1、Ki-67、E-cadherin of SGC7901-pcDNA3.1-GKLF group were lower than that of SGC-7901 and SGC7901-pcDNA3.1 groups ( P <0.05).Conclusion: Transfection with GKLF gene might suppress proliferation and invasion ability of human gastric carcinoma cell line SGC-7901 by downregulation the expressions of Cyclin D1、Ki-67、E-cadherin.
Part 4 Experimental study of the impact of biological behaviors on human gastric carcinoma cell line SGC-7901 by GKLF gene transfection in vivo
Objective:To observe the effects of GKLF gene transfection on growth and metastasis of human gastric carcinoma cell line SGC-7901 xenograft in nude mice,to explore the potential mechanism of GKLF gene in gastric carcinoma and to bring a new method of gene therapy for human gastric carcinoma.Methods: We carried out an in vivo study with 36 BALB/C-nu/nu nude mice which divided into two parts.Every 18 nude mice were randomly divided into 3 groups.SGC7901-pcDNA3.1-GKLF、SGC7901-pcDNA3.1、SGC-7901 were injected into 3 groups nude mice .Every group nude mice injected with the same cell and volume(2×107 cells/200μl/mouse) .In part one, cells were injected into right costal abdomen subcutis of nude mice.The mice were killed 6 weeks later after injection and the changes of weight、volume、latency、state were observed. The expressions of GKLF、Ki-67、E-cadherin、VEGF and CD34 in xenograft tissues were stained by immunohistochemistry(IHC).The microvessel density (MVD) of xenograft tissues were evaluated.The size of tumour、blood stream signal and abdominal cavity were examined for tumour metastasis by ultrasonic.In part two,cells were injected into the tail vein of nude mice.The mice were killed 6 weeks later after injection and lung were examined for tumour metastasis by microscope. Results:Compared with SGC7901-pcDNA3.1、SGC-7901 groups,for SGC7901-pcDNA3.1-GKLF group,the stage of latency lengthened and growth of xenograft were inhibited,and the volume and weight of xenograft tissues were small(P <0.05).GKLF protein of xenograft tissues in SGC7901-pcDNA3.1-GKLF group increased.The expressions of Ki-67、E-cadherin、VEGF and MVD value decreased.The size of xenograft tissues were small, blood stream signal were in stage I.No metastasis sites of lung and abdominal cavity were seen in all nude mice.Conclusion: GKLF gene might inhibit the growth of tumour and reduce the formation of new blood vessel by downregulating the expressions of Ki-67、E-cadherin、VEGF.So GKLF gene has potential application value in clinical of being target of gene therapy.
引文
1.游伟程主编.胃癌.北京:中国医药科技出版社,2006,1-2.
2. Bert V, Kenneth K. Cancer genes and the pathways they control. Nature medicine. 2004,10(8): 789-799.
3.金懋林.胃癌化学治疗的发展与运用.中国肿瘤临床,2000,27(10):792-798.
4. Deng D,El-Rifai W,Ji J,et a1.Hypermethylation of metallothionein-3 CpG island in gastric carcinoma.Carcinogenesis,2003,24(1):25-29.
5. Tanaka H,Yashiro M,Sunami T,et a1.ICAM 2 gene therapy for peritoneal dissemination of scirrhous gastric carcinoma.Clin Cancer Res,2004, 10(14):4885-4892.
6. Carneiro F,Oliveira C,Leite M,et a1.Molecular targets and biological modifiers in gastric cancer.Semin Diagn Pathol, 2008, 25(4):274-287.
7. Yet SF,McA’Nulty MM,Folta SC,et al.Human EZF,a Krüppel-like zinc finger protein,is expressed in vascular endothelial cells and contains transcriptional activation and repression domains.J Biol Chem,1998, 273(2):1026-1031.
8. Shields JM,Christy RJ,Yang VW.Identification and characterization of a gene encoding a gut-enriched Krüppel-like factor expressed during growth arrest.J Biol Chem, 1996, 271(33):20009-20017.
9. Song A,Patel A,Thamatrakoln K,et al.Functional domains and DNA- binding sequences of RFLAT-1/KLF13, a Krüppel-like transcription factor of activated Tlymphocytes.J Biol Chem,2002,277(33):30055-30065.
10. Garrett-Sinha LA,Eberspaecher H,Seldin MF, et al.A gene for a novel zinc-finger protein expressed in differentiated epithelial cells and transiently in certain mesenchymal cells.J Biol Chem,1996,271(49): 31384-31390.
11. Foster KW,Frost AR,McKie-Bell P,et al.Increase of GKLF messenger RNA and protein expression during progression of breast cancer.Cancer Res,2000,60(22): 6488-6495.
12. Ton-That H,Kaestner KH,Shields JM,et al.Expression of the gut-enriched Krüppel-like factor gene during development and intestina1 tumorigenesis.FEBS Lett, 1997, 419(2-3): 239-243.
13. Luo AP,Kong JP,Hu GX,et al.Discovery of Ca2+-relevant and differentiation-associated genes down regulated in esophageal squamous cell carcinoma using cDNA microarray. Oncogene,2004,23(6):1291-1299.
14. Wang N,Liu ZH,Xiu FD,et al.Down-regulation of gut-enriched Krüppel-like factor expression in esophageal cancer.World J Gastroenterol,2002,8(6):966-970.
15. Bianchi F,Hu J,Pelosi G,et al.Lung cancers detected by screening with spiral computed tomography have a malignant phenotype when analyzed by cDNA microarray.ClinCancer Res,2004,10(18 pt 1):6023-6028.
16. Luo J,Dunn T,Ewing C,et al.Gene expression signature of benign prostatic hyperplasia revealed by cDNA microarray analysis. Prostate, 2002,51(3):189-200.
17. Ohnishi S,Ohnami S,Laub F,et al.Downregulation and growth inhibitory effect of epithelial-type Krüppel-like transcription factor KLF4, but not KLF5,in bladder cancer.Biochem Biophys Res Commun,2003,308(2):251-256.
18. Xu J,Lu BJ,Xu FY,et al.Dynamic down-regulation of Krüppel-like factor 4 in colorectal adenoma-carcinoma sequence. Cancer Res Clin Oncol,2008,134(8):891-898.
19. Ghaleb AM,McConnell BB,Nandan MO,et al.Haploin sufficiency of Krüppel -like factor 4 promotes adenomatous polyposis coli dependent intestinal tumorigenesis. Cancer Res,2007,67(15):7147-7154.
20.王楠,刘芝华,丁芳,等.胃肠富集Krüppel样因子表达对食管鳞癌细胞的影响.生物化学与生物物理学报,2003,35(1):55-58.
21.刘红,崔竹梅,李玉军,等.子宫内膜癌组织锌指蛋白KLF4的表达及临床意义.山东医药,2005,45(24):29.
22.左艳,胡若磊,左莉,等.胃肠富集Krüppel样因子在人结直肠肿瘤中的表达.安徽医科大学学报,2006,41(2):178-181.
23.王晓颖,朱延波,林晓珠,等.胰腺导管腺癌Spl、PTEN和KLF4的表达及其与微血管密度的关系.诊断学理论与实践,2007,6(5):427-430.
24.房新辉,杨玉秀,韩双印,等.肝癌组织中KLF4的表达及意义.山东医药,2009,49(1):4-6.
25.吴钊,陈小鱼,张能,等. KLF4蛋白在胃癌组织中的表达及临床意义.癌变、畸变、突变.2009,21(5):388-391.
26. Wei D,Gong W,Kanai M,et a1.Drastic down-regulation of Krüppel-like factor 4 expression is critical in human gastric cancer development and progression.Cancer Res,2005,65(7):2746-2754.
27. Zhao W,Hisamuddin IM,Nandan MO,et al.Identification of Krüppel-like factor 4 as a potential tumor suppressor gene in colorectal cancer.Oncogene,2004,23(2):395-402.
28. Zhang W,Geiman DE,Shields JM,et al.The gut-enriched Krüppel-like factor (Krüppel-like factor 4)mediates the transactivating effect of p53 on the p21WAF1/Cip1 promoter.J Biol Chem,2000,275(24):18391-18398.
29.Yoon HS,Yang VW.Requirement of Krüppel-like factor 4 in preventing entry into mitosis following DNA damage.J Biol Chem,2004,279(6): 5035-5041.
30.Shie JL,Chen ZY,Fu M,et al.Gut-enriched Krüppel-like factor repressses cyclin D1 promoter activity through Sp1 motif.Nucleic Acids Res,2000,28(15):2969-2976.
1. Chen ZY,Shie J,Tseng C.Up-regulation of gut-enriched krüppe1-1ike factor by interferon-γin human colon carcinoma cells.FEBS Lett,2000,477(1):67-72.
2. Zhao W,Hisamuddin IM,Nandan MO, et al.Identification of Krüppel-like factor 4 as a potential tumor suppressor gene in colorectal cancer. Oncogene,2004,23(2):395-402.
3. Tong D, Czerwenka K, Heinze G, et al. Expression of IKLF is a prognostic factor for disease survival and overall survival in patients with breast cancer.Clin Cancer Res,2006,12(8):2442-2448.
4. Lauren P.The two histological main types of gastric carcinoma:diffuse and so-called intestinal type carcinoma.Acta Pathol Microbiol Scand,1965,64(2):331-349.
5. Mullaney PJ,Wadley MS,Hyde C,et al.Appraisal of compliance with the UICC/AJCC staging system in the staging of gastric cancer.Union Inrtional Contra la Cancrum/American Joint Committee on Cancer.Br J Surg,2002,89(11):1405-1408.
6. Wang L,Wei D,Huang S,et al.Transcription factor Sp1 expression is a significant predictor of survival in human gastric cancer.Clinical Cancer Research,2003, 9(17):6371-6380.
7. Jane van Vliet,Linda A.Crofts,Kate G R. Quinlan,et al.Human KLF17 is a new member of the Sp/KLF family of transcription factors.J Genomics, 2006,87(4):474-482.
8. Yet SF,McA’Nulty MM,Folta SC,et al.Human EZF,a Krüppel-like zinc finger protein,is expressed in vascular endothelial cells and contains transcriptional activation and repression domains.J Biol Chem, 1998,273(2):1026-1031.
9. Garrett-Sinha LA,Eberspaecher H,Seldin MF, et al.A gene for a novel zinc-finger protein expressed in differentiated epithelial cells and transiently in certain mesenchymal cells.J Biol Chem,1996,271(49): 31384–31390.
10. Wei DY,Gong WD,Kanai M,et al.Drastic down-regulation of Krüppel-like factor 4 expression is critical in human gastric cancer development and progression.CancerRes,2005,65(7):2746-2754.
11. Shie JL,Chen ZY,Opbrien MJ,et al.Role of gut-enriched Krüppel-like factor in colonic cell growth and differentiation.Am J Physiol Gastrointest Liver Physiol,2000, 279(4): G806-G814.
12. Luo A,Kong J,Hu G,et al.Discovery of Ca2+-relevant and differentiation-associated genes downregulated in esophageal squamous cell carcinoma using cDNA microarray. Oncogene,2004,23(6):1291-1299.
13. Ohnishi S,Ohnami S,Laub F,et al.Downregulation and growth inhibitory effect of epithelial-type Krüppel-like transcription factor KLF4, but not KLF5, in bladder cancer.Biochem Biophys Res Commun,2003,308(2):251-256.
14. Luo J,Dunn T,Ewing C,et al.Gene expression signature of benign prostatic hyperplasia revealed by cDNA microarray analysis. Prostate, 2002,51(3): 189-200.
15. Bianchi F,Hu J,Pelosi G,et al.Lung cancers detected by screening with spiral computed tomography have a malignant phenotype when analyzed by cDNA microarray.Clin Cancer Res,2004,10(18 pt 1):6023-6028.
16. Huang CC,Liu Z,Li X,et al.KLF4 and PCNA identify stages of tumor initiation in a conditional model of cutaneous squamous epithelial neoplasia. Cancer Biol Ther,2005,4(12):1401-1408.
17. Foster KW,Frost AR,McKie-Bell P,et al.Increase of GKLF messenger RNA and protein expression during progression of breast cancer.Cancer Res,2000, 60(22): 6488-6495.
18. Zhao W,Hisamuddin IM,Nandan MO,et al.Identification of Krüppel-like factor 4 as a potential tumor suppressor gene in colorectal cancer.Oncogene,2004,23(2):395-402.
19. Ghaleb AM,McConnell BB,Nandan MO,et al.Haploin sufficiency of Krüppel -like factor 4 promotes adenomatous polyposis coli dependent intestinal tumorigenesis.Cancer Res,2007,67(15):7147-7154.
20. Zhang W,Geiman DE,Shields JM,et al.The gut-enriched Krüppel-like factor(Krüppel-like factor 4)mediates the transactivating effect of p53 on thep21WAF1/Cip1 promoter.J Biol Chem,2000,275(24):18391-18398.
21. Yoon HS,Yang VW.Requirement of Krüppel-like factor 4 in preventing entry into mitosis following DNA damage.J Biol Chem,2004,279(6):5035-5041.
22. Shie JL,Chen ZY,Fu M,et al.Gut-enriched Krüppel-like factor repressses cyclin D1 promoter activity through Sp1 motif.Nucleic Acids Res,2000,28(15):2969-2976.
23. Sogawa K,Imataka H,Yamasaki Y,et al.cDNA cloning and transcriptional properties of a novel GC box-binding protein, BTEB2. Nucleic Acids Res, 1993,21(7):1527-1532.
24. Conkright MD,Wani MA,Anderson KP,et al.A gene encoding an intestinal-enriched member of the Krüppel-like factor family expressed in intestinal epithelial cells. Nucleic Acids Res,1999,27(5):1263-1270.
25. Nandan MO,Yoon HS,ZhaoW,et al.Krüppel-like factor 5 mediates the transforming activity of oncogenic H-Ras.Oncogene.2004:23(19):3404-3413.
26. Chen C,Benjamin MS,Sun X,et al.IKLF promotes cell proliferation and tumorigenesis through gene regulation in the TSU-Pr1 human bladder cancer cell line.Int J Cancer,2006,118(6):1346-1355.
27. Chen C,Bhalala HV,Vessella RL,et al.KLF5 is frequently deleted and down-regulated but rarely mutated in prostate cancer.Prostate.2003;55(2):81-88.
28. ChenC,Bhalala HV,QiaoH,et al.A possible tumor suppressor role of the KLF5 transcription factor in human breast cancer.Oncogene.2002;21(43):6567-6572.
29. Yang Y,Goldstein BG, Chao HH, Katz JP.KLF4 and KLF5 regulate proliferation, apoptosis and invasion in esophageal cancer cells. Cancer Biol &Ther,2005, 11 (4):1216-1221.
30.Sun R,Chen X,Yang VW.Intestinal-enriched Krüppel-like factor (Krüppel-like Factor 5) is a positive regulator of cellular proliferation. J Biol Chem,2001,276(10):6897-6900.
1.刘梅冬,刘瑛,刘俊文,等.KLF4过表达对RAW264.7巨噬细胞和C2C12肌原细胞增殖的影响.生命科学研究,2007,11(3):263-267.
2. Kharas MG,Yusuf I,Scarfone VM,et al.KLF 4 suppresses transformation of pre-B cells by ABL oncogenes.Blood,2007,109(2):747-755.
3. Good KL,Tangye SG.Decreased expression of Krüppel-like factors in memory B cells induces the rapid response typical of secondary antibody responses.Proc Natl Acad Sci USA,2007,104(33):13420-13425.
4. Luo AP,Kong JP,Hu GX,et al.Discovery of Ca2+-relevant and differentiation-associated genes down regulated in esophageal squamous cell carcinoma using cDNA microarray.Oncogene,2004,23(6):1291-1299.
5. Wang N,Liu ZH,Xiu FD,et al.Down-regulation of gut-enriched Krüppel-like factor expression in esophageal cancer.World J Gastroenterol,2002,8(6):966-970.
6. Xu J,Lu BJ,Xu FY,et al.Dynamic down-regulation of Krüppel-like factor 4 in colorectal adenoma-carcinoma sequence. Cancer Res Clin Oncol, 2008,134 (8):891-898.
7.房新辉,杨玉秀,韩双印,等.肝癌组织中KLF4的表达及意义.山东医药, 2009,49(1):4-6.
8. Bianchi F,Hu J,Pelosi G,et al.Lung cancers detected by screening with spiral computed tomography have a malignant phenotype when analyzed by cDNA microarray.Clin Cancer Res,2004,10(18 pt 1):6023-6028.
9.刘红,崔竹梅,李玉军,等.子宫内膜癌组织锌指蛋白KLF4的表达及临床意义.山东医药,2005,45(24):29.
10. Luo J,Dunn T,Ewing C,et al.Gene expression signature of benign prostatic hyperplasia revealed by cDNA microarray analysis. Prostate, 2002,51(3):189-200.
11. Ohnishi S,Ohnami S,Laub F,et al.Downregulation and growth inhibitory effect of epithelial-type Krüppel-like transcription factor KLF4, but not KLF5,in bladder cancer.Biochem Biophys Res Commun,2003,308(2):251-256.
12. Zhang L,Wali A,Ramana CV,et al.Cell growth inhibition by okadaic acid involves gut-enriched Krüppel-like factor mediated enhanced expression of c-Myc.Cancer Res,2007,67(21):10198-10206.
13. Chen XM,Whitney EM,Gao SY,et al.Transcriptional profiling of Krüppel-like factor 4 reveals a function in cell cycle regulation and epithelial differentiation.J MolBiol,2003,326(3):665-677.
14. Shields JM,Christy RJ,Yang VW.Identification and characterization of a gene encoding a gut-enriched Krüppel-like factor expressed during growth arrest.J Biol Chem,1996,271(33):20009-20017.
15. Rolland AP. Form genes to gene medicines:recent advances in nonviral gene delivery. Crit Rev Ther Grug Carrier Syst. 1998,15(2):143-198.
16. Spencer SC. Electroporation technique of DNA transfection. Applied Biochemistry and Biotechnology, 1993,42(1):75-82.
17.Walters DK,Jelinek DF.The effectiveness of double-stranded short inhibitory RNAs(siRNAs) may depend on the method of transfection.Antisense Nucleic Acid Drug Dev, 2002,12(6):411-418.
18. Wang D,Jing NH,Lin QS.Strearylamine liposome as a new efficient reagent for DNA transfection of eukaryotic cells.Biochem Biophy Res Commu,1996,226(2):450-455.
19. Gilmore IR,Fox SP,Hollins AJ,et al.Delivery strategies for siRNA-mediated gene silencing.Curr Drug Deliv.2006,3(2):147-155.
20. Byrnes AP,Rusby JE,Wood MJA,et al.Adenovirus gene transfer causes inflammation in the brain. Neuroscience,1995,66(4):1015-1024.
21.Liu CM,Liu DP,Dong WJ,et al.Retrovirus vector-mediated stable gene silencing in human cell.Biochemical and Biophysical Research Communications,2004,313(3): 716-720.
22. Li S,Ma Z. Nonviral gene therapy. Curr Gene Ther,2001,1(2):201-226.
23. Dalby B,Cates S,Harris A,et al.Advanced transfection with lipofectamine 2000 reagent: primary neurons, siRNA, and high-througuput applications.Methods,2004,33(2):95-103.
1. Shields JM,Christy RJ,Yang VW.Identification and characterization of a gene encoding a gut-enriched Kruppel-like factor expressed during growth arrest.J Biol Chem,1996,271(33):20009-20017.
2. Yet SF,McA’Nulty MM,Folta SC,et al.Human EZF,a Krüppel-like zinc finger protein,is expressed in vascular endothelial cells and contains transcriptional activation and repression domains.J Biol Chem,1998,273(2):1026-1031.
3. Ton-That H,Kaestner KH,Shields JM,et al.Expression of the gut-enriched Krüppel-like factor gene during development and intestina1 tumorigenesis.FEBS Lett,1997,419(2-3):239-243.
4.吴晓英,陈卫昌.人胃腺癌组织中KLF4表达及临床意义.苏州医学,2008,31(2):71-75.
5. Kawada K,Yonei T,Ueoka H,et al.Comparison of chemosensitivity tests: clonogenic assay versus MTT assay.Acta Med Okayama,2002,56(3):129-134.
6.韩梅,陈卫昌,严苏.重组人白细胞介素24蛋白的纯化及其对胃癌细胞凋亡的影响.苏州大学学报(医学版),2006,26(3):362-366.
7. Shie JL,Chen ZY,OpBrien MJ,et al.Role of gut-enriched Krüppel-like factor in colonic cell growth and differentiation.Am J Physiol Gastrointest Liver Physiol,2000,279(4):G806～G814.
8.王渝,柯昌庶,赵秋,等.E-cadherin,β-catenin,Cyclin D1在胃腺癌中的表达及临床意义.世界华人消化杂志,2007,15(4): 403-407.
9.王桂兰,陈莉,李杏玉,等.NET21、Ki67和CD34在胃癌组织中的表达及其临床病理意义.肿瘤防治研究,2009,36(3):216-220.
10. Wang N,Liu ZH,Xiu FD,et al.Down-regulation of gut-enriched Krüppel-like factor expression in esophageal cancer.World J Gastroenterol,2002,8(6):966-970.
11. Van Seuningen I,PerraisM,Pigny P,et al.Sequence of the 5′- flanking region and promoter activity of the human mucin gene MUC5B in different phenotypes of colon cancer cells. Biochem J,2000,348 Pt 3:675-686.
12. Miller KA,Eklund EA,Peddinghaus ML,et al.Krüppel-like factor 4 regulates laminin alpha3A expression in mammary epithelial cells.J Biol Chem, 2001, 276(46):42863-42868.
13. Zhang W,Geiman DE,Shields JM,et al.The gutenriched Krüppel-like factor (Krüppel-like factor 4)mediates the transactivating effect of p53 on the p21WAF1/Cip1 promoter.J Biol Chem,2000,275(24):18391-18398.
14. Chen X,Johns DC,Geiman DE,et al.Krüppel-like factor 4(gut-enriched Krüppel-like factor)inhibits cell proliferation by blocking G1/S progression of the cell cycle.J Biol Chem,2001,276(32):30423-30428.
1.吴学文,王邦茂,曹晓沧.hTR反义PS—ODN联合顺铂对人胃癌裸鼠皮下移植瘤作用的体内研究.肿瘤研究与临床,2005,17(4):226-229.
2. Alder DD,Carson PL,Rubin JM,et al.Doppler ultrasound flowimaging in the study of breast canner:Pre-liminary findings.Ultrasound Med Biol,1990,16(6):553-559.
3.郑金锋,曹永成,耿明,等.钙粘素、Ki67和p16在人脑胶质瘤中的表达及意义.中国临床神经外科杂志,2006,11(8):473-475.
4. Birner P,Schindle M,Obermair A,et al.Overexpression of Hypoxia -inducible Factor 1αIs a Marker for an Unfavorable Prognosis in Early -Stage Invasive Cervical Cancer. Cancer Res,2000,60(17):4693-4696.
5. Weidner N.Intratumor microvessel density as a prognostic factor in cancer.Am J Pathol,1995,147(1):9-19.
6.万远廉,戎龙,刘玉树,等.组织因子对大肠癌细胞侵袭及血行转移的影响.中华外科杂志,2005,43(19):1265-1267.
7.肖航,恽时锋,刘年双主编.实验动物科学与应用.南京:凤凰出版传媒集团江苏科学技术出版社,2008,130-137.
8. Xie K,Wei D,Huang S.Transcription anti-angiogenesis therapy of human pancreatic cancer.Cytokine Growth Factor Rev,2006,l7(3):l47-l56.
9. Hicklin DJ, Ellis LM. Role of the vascular endothelial growth factor pathway in tumor growth and angiogenesis Journal clinical oncology, 2005,23(5):1011-1027.
10. Gerber HP, Ferrara N. The role of VEGF in normal and neoplastic hematopoiesis.J Mol Med,2003,81(1):20-31.
11. Vermeulen PB, Colpaert C, Salgado R, et al. Liver metastases from colorectal adenocarcinomas grow in three patterns with different angiogenesis and desmoplasia.J Pathol,2001,195(3):336-342.
12. Ferrara N.Vascular Endothelial Growth Factor as a Target for Anticancer Therapy.Oncologist,2004,9(suppl 1):2-10.
13. Fang J, Shing Y, Wiederschain D, et al.Matrix metalloproteinase-2 is required for the switch to the angiogenic phenotype in a tumor model. PNAS,2000,97(8):3884-3889.
14. Kahashima A,Maehara Y,Kakeji Y,et al.Overexpression of vascular endothelial growth factor C is related to lymphogenous metastasis in early gastric carcinoma. Oncology,2001,60(2):146-150.
15.郑海,陈明,张景辉,等.核转录因子KLF4与VEGF启动子上游DNA序列相互作用研究.华中科技大学学报(医学版),2008,37(6):808-811.
[1] Jane van Vliet,Linda A.Crofts,Kate G R. Quinlan,et al.Human KLF17 is a new member of the Sp/KLF family of transcription factors.J Genomics, 2006,87(4):474-482.
[2] Yet SF,McA’Nulty MM,Folta SC,et al.Human EZF,a Krüppel-like zinc finger protein,is expressed in vascular endothelial cells and contains transcriptional activation and repression domains.J Biol Chem, 1998,273(2):1026-1031.
[3] Jenkins TD,Opitz OG,Okano J,Rustgi AK.Transactivation of the human keratin 4 and Epstein-Barr virus ED-L2 promoters by gut-enriched Krüppel-like factor.J Biol Chem,1998,273(17):10747-10754.
[4] Shie JL,Chen ZY,OpBrien MJ,et al.Role of gut-enriched Krüppel-like factor in colonic cell growth and differentiation.Am J Physiol Gastrointest Liver Physiol, 2000, 279(4): G806～G814.
[5] Shields JM,Christy RJ,Yang VW.Identification and characterization of a gene encoding a gut-enriched Krüppel-like factor expressed during growth arrest.J Biol Chem, 1996, 271(33):20009-20017.
[6] Song A,Patel A,Thamatrakoln K,et al.Functional domains and DNA- binding sequences of RFLAT-1/KLF13, a Krüppel-like transcription factor of activated Tlymphocytes.J Biol Chem,2002,277(33):30055-30065.
[7] Evans PM,Zhang W,Chen X,Yang J,et al.Krüppel-like factor 4 is acetylated by p300 and regulates gene transcription via modulation of histone acetylation .J Biol Chem,2007,282(47):33994-34002.
[8] Shields JM,Yang VW.Two potent nuclear 1ocalization signals in The gut-enriched Krüppel-like factor define a subfamily of closely related Krüppe1 proteins.J Biol Chem,1997,272(29):18504-18507.
[9] Garrett-Sinha LA,Eberspaecher H,Seldin MF, et al.A gene for a novel zinc-finger protein expressed in differentiated epithelial cells and transiently in certain mesenchymal cells.J Biol Chem,1996,271(49): 31384-31390.
[10] Panigada M,Porcellini S,Sutti F,et al.GKLF in thymus epithelium as adevelopmentally regulated element of thymocyte-stroma cross-talk. Mech Dev,1999, 81(1-2):103-113.
[11] Behr R and Kaestner KH. Developmental and cell type-specific expression of the zinc finger transcription factor Krüppel-like factor 4 (Klf4) in postnatal mouse testis.Mech Dev,2002,115(1-2):167-169.
[12] Ohnishi S,Laub F,Matsumoto N,et al.Developmental expression of the mouse gene coding for the Krüppel-like transcription factor KLF4.Dev Dyn, 2000,217 (4):421 -429.
[13] Chiambaretta F,De Graeve F,Turet G,et al.Cell and tissue specific expression of human Krüppel-like transcription factors in human ocular surface.Mol Vis,2004, 10:901-909.
[14] Foster KW,Frost AR,McKie-Bell P,et al.Increase of GKLF messenger RNA and protein expression during progression of breast cancer.Cancer Res,2000, 60(22): 6488-6495.
[15] Hamik A,Lin Z,Kumar A,et al.Krüppel-like factor 4 regulates endothelial inflame -mation.J Biol Chem,2007,282(18):13769-13779.
[16]刘梅冬,刘瑛,刘俊文,等.KLF4过表达对RAW264.7巨噬细胞和C2C12肌原细胞增殖的影响.生命科学研究,2007,11(3):263-267.
[17] Liu JW,Zhang H,Liu Y,et al.KLF4 regulates the expression of interleukin-10 in RAW264.7 macrophages.Biochem Biophys Res Commun,2007, 362(3):575-581.
[18] Liu Y,Zhao J,Liu JW,et al.Up-regulation of the constitutively expressed HSF73 by KLF4. Cell Stress Chaperones,2008,13(3):337-345.
[19] Liu MD,Liu Y,Liu JW,et al.Effect of Krüppel-like factor 4 overexpression on heat stress-induced apoptosis of Raw264.7 macrophages.Zhong Nan Da Xue Xue Bao(Yi Xue Ban),2007,32(6):1002-1006.
[20] Katz JP,Perreault N,Goldstein BG,et al.The zinc-finger transcription factor Klf4 is required for terminal differentiation of goblet cells in the colon. Development, 2002, 129(11):2619-2628.
[21] Segre JA,Bauer C,Fuchs E.Klf4 is a transcription factor required for establishing the barrier function of the skin.Nat Genet,1999, 22(4):356-360.
[22] Swamynathan SK,Katz JP,Kaestner KH,et al.Conditional deletion of mouse Klf4 gene results in corneal epithelial fragility , stromal edema and loss of conjunctival goblet cells.Mol Cell Biol,2007,27(1):182-194.
[23] Luo TH,Zhao Y,Li G,et a1.Differential expression of genes in omental fat of normal weight and obese subjects and obese diabetic patient using cDNA microarray.上海第二医科大学学报(英文版),2007,19(1):1-7,36.
[24]吴铃,赵萸,骆天红,等.转录因子KLF4在脂肪细胞分化过程中的表达变化.上海医学,2007,30(12):930-932.
[25] Kharas MG,Yusuf I,Scarfone VM,et al.KLF 4 suppresses transformation of pre-B cells by ABL oncogenes.Blood,2007,109(2):747-755.
[26] Good KL,Tangye SG.Decreased expression of Kruppel-like factors in memory B cells induces the rapid response typical of secondary antibody responses.Proc Natl Acad Sci USA,2007,104(33):13420-13425.
[27] Wei D,Kanai M,Huang S,et al.Emerging role of KLF4 in Human gastrointestinal cancer.Carcinogenesis,2006,27(1):23-31.
[28] Shie JL,Chen ZY,Fu M,et al.Gut-enriched Krüppel-like factor repressses cyclin D1 promoter activity through Sp1 motif.Nucleic Acids Res,2000,28(15):2969-2976.
[29]王晓颖,朱延波,林晓珠,等.胰腺导管腺癌Spl、PTEN和KLF4的表达及其与微血管密度的关系。诊断学理论与实践,2007,6(5):427-430.
[30] Mahatan CS,Kaestner KH,Geiman DE,et al.Characterization of the structure and regulation of the murine gene encoding gut-enriched Krüppel-like factor(Krüppel-like factor 4).Nucleic Acids Res 1999,27(23):4562-4569.
[31] Wang N,Liu ZH,Ding F,et al.Down-regulation of Gut-enriched Krüppel-like factor expression in esophageal cancer.World J Gastroenterol,2002,8(6):966-970.
[32] Chen ZY,Shie JL,Tseng CC.Up-regulation of gut-enriched krüppel-like factor by interferon-γ,in human colon carcinoma cells.FEBS Lett, 2000,477(1):67-72.
[33] Chen ZY,Shie JL,Tseng CC.STAT1 is required for IFN-gamma-mediated gut- enriched Kruppel-like factor expression.Exp Cell Res,2002, 281(1):19-27.
[34] Zhang W,Geiman DE,Shields JM,et al.The gut-enriched Krüppel-like factor (Krüppel-like factor 4)mediates the transactivating effect of p53 on the p21WAF1/Cip1 promoter.J Biol Chem,2000,275(24):18391-18398.
[35] Brembeck FH,Rustgi AK.The tissue-dependent keratin 19 gene transcription is regulated by GKLF/KLF4 and Sp1.J Biol Chem, 2000,275(36):28230-28239.
[36] Feinberg MW,Wara AK,Cao Z,et al.The Krüppel-like factor KLF4 is a critical regulator of monocyte differentiation.EMBO J,2007, 26(18):4138-4148.
[37] Zhang W,Shields JM,Sogawa K,et al.The gut-enriched Krüppel-like factor suppresses the activity of the CYPIA1 promoter in an Spl-dependent fashion.J Biol Chem, 1998,273(28):17917-17925.
[38] Rowland BD,Bernards R,Peeper DS.The KLF4 tumour suppressor is a transcriptional repressor of p53 that acts as a context-dependent oncogene. Nat Cell Biol, 2005, 7(11):1074-1082.
[39] Katz JP,Perreault N,Goldstein BG,et al. Loss of Klf4 in mice causes altered proliferation and differentiation and precancerous changes in the adult stomach. Gastroenterology,2005,128(4):935-945.
[40] Yoon HS,Yang VW.Requirement of Krüppel-like factor 4 in preventing entry into mitosis following DNA damage.J Biol Chem,2004, 279(6):5035-5041.
[41] Chen XM,Whitney EM,Gao SY,et al.Transcriptional profiling of Krüppel-like factor 4 reveals a function in cell cycle regulation and epithelial differentiation.J Mol Biol,2003,326(3):665-677.
[42] Ton-That H,Kaestner KH,Shields JM,et al.Expression of the gut-enriched Krüppel-like factor gene during development and intestina1 tumorigenesis.FEBS Lett, 1997, 419(2-3):239-243.
[43] Luo AP,Kong JP,Hu GX,et al.Discovery of Ca2+-relevant and differentiation -associated genes down regulated in esophageal squamous cell carcinoma usingcDNA microarray.Oncogene,2004,23(6):1291-1299.
[44] Wang N,Liu ZH,Xiu FD,et al.Down-regulation of gut-enriched Krüppel-like factor expression in esophageal cancer.World J Gastroenterol,2002,8(6):966-970.
[45] Bianchi F,Hu J,Pelosi G,et al.Lung cancers detected by screening with spiral computed tomography have a malignant phenotype when analyzed by cDNA microarray.Clin Cancer Res,2004,10(18 pt 1):6023-6028.
[46] Luo J,Dunn T,Ewing C,et al.Gene expression signature of benign prostatic hyperplasia revealed by cDNA microarray analysis.Prostate, 2002,51(3): 189-200.
[47] Ohnishi S,Ohnami S,Laub F,et al.Downregulation and growth inhibitory effect of epithelial-type Krüppel-like transcription factor KLF4, but not KLF5,in bladder cancer.Biochem Biophys Res Commun,2003,308(2):251-256.
[48] Xu J,Lu BJ,Xu FY,et al.Dynamic down-regulation of Krüppel-like factor 4 in colorectal adenoma-carcinoma sequence. Cancer Res Clin Oncol, 2008, 134 (8):891-898.
[49] Ghaleb AM,McConnell BB,Nandan MO,et al.Haploin sufficiency of Krüppel -like factor 4 promotes adenomatous polyposis coli dependent intestinal tumorigenesis. Cancer Res,2007,67(15):7147-7154.
[50]刘红,崔竹梅,李玉军,等.子宫内膜癌组织锌指蛋白KLF4的表达及临床意义。山东医药,2005,45(24):29.
[51]左艳,胡若磊,左莉,等.胃肠富集Kruppel样因子在人结直肠肿瘤中的表达。安徽医科大学学报,2006,41(2):178-181.
[52]房新辉,杨玉秀,韩双印,等.肝癌组织中KLF4的表达及意义。山东医药,2009,49(1):4-6.
[53] Wei D,Gong W ,Kanai M ,et a1. Drastic down-regulation of Krüppel-like factor 4 expression is critical in human gastric cancer development and progression.Cancer Res,2005,65(7):2746-2754.
[54] Cho YG,Song JH,Kim CJ,et al. Genetic and epigenetic analysis of the KLF4 gene in gastric cancer. APMIS,2007,115(7):802-808.
[55] Zhao W,Hisamuddin IM,Nandan MO,et al.Identification of Krüppel-like factor 4 as a potential tumor suppressor gene in colorectal cancer.Oncogene,2004,23(2):395-402.
[56] Huang CC,Liu Z,Li X,et al.KLF4 and PCNA identify stages of tumor initiation in a conditional model of cutaneous squamous epithelial neoplasia. Cancer Biol Ther,2005,4(12):1401-1408.
[57] Pandya AY,Talley LI,Frost AR,et al.Nuclear localization of KLF 4 is associated with an aggressive phenotype in early stage breast cancer.Clin Cancer Res, 2004, 10(8):2709-2719.
[58] Zhang L,Wali A,Ramana CV,et al.Cell growth inhibition by okadaic acid involves gut-enriched Krüppel-like factor mediated enhanced expression of c-Myc.Cancer Res,2007,67(21):10198-10206.
[1] Nishimura T.Total number of genome alterations in sporadic gastrointestinal cancer inferred from pooled analyses in the literature.Tumour Biol,2008,29(6):343-350.
[2] Wen SF,Xie L,McDonald M,et a1.Development and vaildation of sensitive assays to quantitate gene expression after p53 gene therapy and paclitaxel chemotherapy using in vivo dosing in tumor xenograft models.Cancer Gene Ther,2000,7(11):1469-1480.
[3] Ohashi M,Kanai F,Ueno H,et a1.Adenovirus mediated p53 tumour suppressor gene therapy for human gastric cancer cells in vitro and in vivo.Gut,1999,44(3):366-371.
[4] Huh JJ,Wolf JK,Fightmaster DL,et a1.Transduction of adenovirus-mediated wild-type p53 after radiotherapy in human cervical cancer cells.Gynecol Oncol, 2003, 89(2): 243-250.
[5] Bouvet M,Ellis LM,Nishizaki M,et a1.Adenovirus-mediated wild-type p53 gene transfer down-regulates vascular endothelial growth factor expression and inhibits angiogenesisin human colon cancer.Cancer Res,1998,58(11):2288-2292.
[6] Tamura G.Alterations of tumor suppressor and tumor-related genes in the development and progression of gastric cancer.World J Gastroenterology,2006,12(2):192-198.
[7] Jeong YW,Kim KS,Oh JY,et a1.Exogenous wild-type P16INK4A gene induces delayed cell proliferation and promotes chemosen-sitivity through decreased pRB and increased E2F-l expressions.Int J Mol Med, 2003,12(1):61-65.
[8] Kim R,Emi M,Tanabe K,et a1.Preclinical evaluation of antisence Bcl-2 as a chemosensitizer for patients with gastric carcinoma.Cancer,2004,101(10): 2177-2186.
[9]赵亮,赵家宏,孙凌宇,等.RNA干扰技术沉默Star3基因对胃癌细胞SGC7901生物学行为影响的实验研究.中国肿瘤临床,2008,35(6):348-352.
[10] Wei SJ,Chao Y,Hung YM,et a1.S- and G2-phase cell cycle arrests and apeptosis induced by ganciclovir in murine melanoma cells transduced with herpes simplex virus thymidine kinase.Exp Cell Res,1998,241(1):66-75.
[11] Yoshida K,Kawami H,Yamaguchi Y,et a1.Retrovirallytrailsmitted gene therapy forgastric carcinoma using herpes simplex virus thymidine kinase gene. Cancer, 1995, 75(6):1467-1471.
[12] Wiewrodt R,Amin K,Kiefer M,et a1.Adenovirus-mediated gene transfer of enhanced herpes simplex virus thymidine kinase mutants improves prodrug-mediated tumor cell killing.Cancer Gene Ther,2003,10(5):353-364.
[13] Van Dillen IJ,Mulder NH,Vaalburg W,et a1.Influence of the bystander efect on HSV-tk/GCV gene therapy a review.Curt Gene Ther,2002, 2(3):307-322.
[14] Ueda K,Iwahashi M,Nakamori M,et a1.Carcinoembryonic Antigen-specific suicide gene therapy of cytosine deaminase/5-fluorocytosine enhanced by the cre/loxP system in the orthotopic gastric carcinoma model.Cancer Res,2001,61(16):6158-6162.
[15] Kono K,Takahashi A,Sugai H,et al.Dendritic cells pulsed with HER-2/neu-derived peptides can induce specific T-cell responses in patients with gastric cancer.Clin Cancer Res,2002,8(11):3394-3400.
[16] Kosaka K,Yashiro M,Sakate Y,et a1.CD80 gene therapy for lymph node involvement by gastric carcinoma.Int J Oncol,2004,25(5):1319-l325.
[17] Tanaka H,Yashiro M,Sunami T,et a1.ICAM-2 gene therapy for peritoneal dissemination of scirrhous gastric carcinoma.Clin Cancer Res,2004,10(14): 4885-4892.
[18] Kakeji Y,Maehara Y,Sumiyoshi Y,et a1.Angiogenesls as a target for gastric cancer.Surgery,2002,131(1 Suppl):S48-54.
[19] Sako A,Kitayama J,Koyama H,et a1.Transduction of soluble Flt-1 gene to peritoneal mesothelial cells can efectively suppress peritoneal metastasis of gastric cancer.Cancer Res,2004,64(10):3624-3628.
[20] Stoeltzing O,Mccary MF,Key JS,et a1.Role of hypoxia indueible factor-l alpha in gastric cancer cell growth,angiogenesis and vessel maturation.J Natl Cancer Inst,2004,96(10):946-956.
2. Bert V, Kenneth K. Cancer genes and the pathways they control. Nature medicine. 2004,10(8): 789-799.
3.金懋林.胃癌化学治疗的发展与运用.中国肿瘤临床,2000,27(10):792-798.
4. Deng D,El-Rifai W,Ji J,et a1.Hypermethylation of metallothionein-3 CpG island in gastric carcinoma.Carcinogenesis,2003,24(1):25-29.
5. Tanaka H,Yashiro M,Sunami T,et a1.ICAM 2 gene therapy for peritoneal dissemination of scirrhous gastric carcinoma.Clin Cancer Res,2004, 10(14):4885-4892.
6. Carneiro F,Oliveira C,Leite M,et a1.Molecular targets and biological modifiers in gastric cancer.Semin Diagn Pathol, 2008, 25(4):274-287.
7. Yet SF,McA’Nulty MM,Folta SC,et al.Human EZF,a Krüppel-like zinc finger protein,is expressed in vascular endothelial cells and contains transcriptional activation and repression domains.J Biol Chem,1998, 273(2):1026-1031.
8. Shields JM,Christy RJ,Yang VW.Identification and characterization of a gene encoding a gut-enriched Krüppel-like factor expressed during growth arrest.J Biol Chem, 1996, 271(33):20009-20017.
9. Song A,Patel A,Thamatrakoln K,et al.Functional domains and DNA- binding sequences of RFLAT-1/KLF13, a Krüppel-like transcription factor of activated Tlymphocytes.J Biol Chem,2002,277(33):30055-30065.
10. Garrett-Sinha LA,Eberspaecher H,Seldin MF, et al.A gene for a novel zinc-finger protein expressed in differentiated epithelial cells and transiently in certain mesenchymal cells.J Biol Chem,1996,271(49): 31384-31390.
11. Foster KW,Frost AR,McKie-Bell P,et al.Increase of GKLF messenger RNA and protein expression during progression of breast cancer.Cancer Res,2000,60(22): 6488-6495.
12. Ton-That H,Kaestner KH,Shields JM,et al.Expression of the gut-enriched Krüppel-like factor gene during development and intestina1 tumorigenesis.FEBS Lett, 1997, 419(2-3): 239-243.
13. Luo AP,Kong JP,Hu GX,et al.Discovery of Ca2+-relevant and differentiation-associated genes down regulated in esophageal squamous cell carcinoma using cDNA microarray. Oncogene,2004,23(6):1291-1299.
14. Wang N,Liu ZH,Xiu FD,et al.Down-regulation of gut-enriched Krüppel-like factor expression in esophageal cancer.World J Gastroenterol,2002,8(6):966-970.
15. Bianchi F,Hu J,Pelosi G,et al.Lung cancers detected by screening with spiral computed tomography have a malignant phenotype when analyzed by cDNA microarray.ClinCancer Res,2004,10(18 pt 1):6023-6028.
16. Luo J,Dunn T,Ewing C,et al.Gene expression signature of benign prostatic hyperplasia revealed by cDNA microarray analysis. Prostate, 2002,51(3):189-200.
17. Ohnishi S,Ohnami S,Laub F,et al.Downregulation and growth inhibitory effect of epithelial-type Krüppel-like transcription factor KLF4, but not KLF5,in bladder cancer.Biochem Biophys Res Commun,2003,308(2):251-256.
18. Xu J,Lu BJ,Xu FY,et al.Dynamic down-regulation of Krüppel-like factor 4 in colorectal adenoma-carcinoma sequence. Cancer Res Clin Oncol,2008,134(8):891-898.
19. Ghaleb AM,McConnell BB,Nandan MO,et al.Haploin sufficiency of Krüppel -like factor 4 promotes adenomatous polyposis coli dependent intestinal tumorigenesis. Cancer Res,2007,67(15):7147-7154.
20.王楠,刘芝华,丁芳,等.胃肠富集Krüppel样因子表达对食管鳞癌细胞的影响.生物化学与生物物理学报,2003,35(1):55-58.
21.刘红,崔竹梅,李玉军,等.子宫内膜癌组织锌指蛋白KLF4的表达及临床意义.山东医药,2005,45(24):29.
22.左艳,胡若磊,左莉,等.胃肠富集Krüppel样因子在人结直肠肿瘤中的表达.安徽医科大学学报,2006,41(2):178-181.
23.王晓颖,朱延波,林晓珠,等.胰腺导管腺癌Spl、PTEN和KLF4的表达及其与微血管密度的关系.诊断学理论与实践,2007,6(5):427-430.
24.房新辉,杨玉秀,韩双印,等.肝癌组织中KLF4的表达及意义.山东医药,2009,49(1):4-6.
25.吴钊,陈小鱼,张能,等. KLF4蛋白在胃癌组织中的表达及临床意义.癌变、畸变、突变.2009,21(5):388-391.
26. Wei D,Gong W,Kanai M,et a1.Drastic down-regulation of Krüppel-like factor 4 expression is critical in human gastric cancer development and progression.Cancer Res,2005,65(7):2746-2754.
27. Zhao W,Hisamuddin IM,Nandan MO,et al.Identification of Krüppel-like factor 4 as a potential tumor suppressor gene in colorectal cancer.Oncogene,2004,23(2):395-402.
28. Zhang W,Geiman DE,Shields JM,et al.The gut-enriched Krüppel-like factor (Krüppel-like factor 4)mediates the transactivating effect of p53 on the p21WAF1/Cip1 promoter.J Biol Chem,2000,275(24):18391-18398.
29.Yoon HS,Yang VW.Requirement of Krüppel-like factor 4 in preventing entry into mitosis following DNA damage.J Biol Chem,2004,279(6): 5035-5041.
30.Shie JL,Chen ZY,Fu M,et al.Gut-enriched Krüppel-like factor repressses cyclin D1 promoter activity through Sp1 motif.Nucleic Acids Res,2000,28(15):2969-2976.
1. Chen ZY,Shie J,Tseng C.Up-regulation of gut-enriched krüppe1-1ike factor by interferon-γin human colon carcinoma cells.FEBS Lett,2000,477(1):67-72.
2. Zhao W,Hisamuddin IM,Nandan MO, et al.Identification of Krüppel-like factor 4 as a potential tumor suppressor gene in colorectal cancer. Oncogene,2004,23(2):395-402.
3. Tong D, Czerwenka K, Heinze G, et al. Expression of IKLF is a prognostic factor for disease survival and overall survival in patients with breast cancer.Clin Cancer Res,2006,12(8):2442-2448.
4. Lauren P.The two histological main types of gastric carcinoma:diffuse and so-called intestinal type carcinoma.Acta Pathol Microbiol Scand,1965,64(2):331-349.
5. Mullaney PJ,Wadley MS,Hyde C,et al.Appraisal of compliance with the UICC/AJCC staging system in the staging of gastric cancer.Union Inrtional Contra la Cancrum/American Joint Committee on Cancer.Br J Surg,2002,89(11):1405-1408.
6. Wang L,Wei D,Huang S,et al.Transcription factor Sp1 expression is a significant predictor of survival in human gastric cancer.Clinical Cancer Research,2003, 9(17):6371-6380.
7. Jane van Vliet,Linda A.Crofts,Kate G R. Quinlan,et al.Human KLF17 is a new member of the Sp/KLF family of transcription factors.J Genomics, 2006,87(4):474-482.
8. Yet SF,McA’Nulty MM,Folta SC,et al.Human EZF,a Krüppel-like zinc finger protein,is expressed in vascular endothelial cells and contains transcriptional activation and repression domains.J Biol Chem, 1998,273(2):1026-1031.
9. Garrett-Sinha LA,Eberspaecher H,Seldin MF, et al.A gene for a novel zinc-finger protein expressed in differentiated epithelial cells and transiently in certain mesenchymal cells.J Biol Chem,1996,271(49): 31384–31390.
10. Wei DY,Gong WD,Kanai M,et al.Drastic down-regulation of Krüppel-like factor 4 expression is critical in human gastric cancer development and progression.CancerRes,2005,65(7):2746-2754.
11. Shie JL,Chen ZY,Opbrien MJ,et al.Role of gut-enriched Krüppel-like factor in colonic cell growth and differentiation.Am J Physiol Gastrointest Liver Physiol,2000, 279(4): G806-G814.
12. Luo A,Kong J,Hu G,et al.Discovery of Ca2+-relevant and differentiation-associated genes downregulated in esophageal squamous cell carcinoma using cDNA microarray. Oncogene,2004,23(6):1291-1299.
13. Ohnishi S,Ohnami S,Laub F,et al.Downregulation and growth inhibitory effect of epithelial-type Krüppel-like transcription factor KLF4, but not KLF5, in bladder cancer.Biochem Biophys Res Commun,2003,308(2):251-256.
14. Luo J,Dunn T,Ewing C,et al.Gene expression signature of benign prostatic hyperplasia revealed by cDNA microarray analysis. Prostate, 2002,51(3): 189-200.
15. Bianchi F,Hu J,Pelosi G,et al.Lung cancers detected by screening with spiral computed tomography have a malignant phenotype when analyzed by cDNA microarray.Clin Cancer Res,2004,10(18 pt 1):6023-6028.
16. Huang CC,Liu Z,Li X,et al.KLF4 and PCNA identify stages of tumor initiation in a conditional model of cutaneous squamous epithelial neoplasia. Cancer Biol Ther,2005,4(12):1401-1408.
17. Foster KW,Frost AR,McKie-Bell P,et al.Increase of GKLF messenger RNA and protein expression during progression of breast cancer.Cancer Res,2000, 60(22): 6488-6495.
18. Zhao W,Hisamuddin IM,Nandan MO,et al.Identification of Krüppel-like factor 4 as a potential tumor suppressor gene in colorectal cancer.Oncogene,2004,23(2):395-402.
19. Ghaleb AM,McConnell BB,Nandan MO,et al.Haploin sufficiency of Krüppel -like factor 4 promotes adenomatous polyposis coli dependent intestinal tumorigenesis.Cancer Res,2007,67(15):7147-7154.
20. Zhang W,Geiman DE,Shields JM,et al.The gut-enriched Krüppel-like factor(Krüppel-like factor 4)mediates the transactivating effect of p53 on thep21WAF1/Cip1 promoter.J Biol Chem,2000,275(24):18391-18398.
21. Yoon HS,Yang VW.Requirement of Krüppel-like factor 4 in preventing entry into mitosis following DNA damage.J Biol Chem,2004,279(6):5035-5041.
22. Shie JL,Chen ZY,Fu M,et al.Gut-enriched Krüppel-like factor repressses cyclin D1 promoter activity through Sp1 motif.Nucleic Acids Res,2000,28(15):2969-2976.
23. Sogawa K,Imataka H,Yamasaki Y,et al.cDNA cloning and transcriptional properties of a novel GC box-binding protein, BTEB2. Nucleic Acids Res, 1993,21(7):1527-1532.
24. Conkright MD,Wani MA,Anderson KP,et al.A gene encoding an intestinal-enriched member of the Krüppel-like factor family expressed in intestinal epithelial cells. Nucleic Acids Res,1999,27(5):1263-1270.
25. Nandan MO,Yoon HS,ZhaoW,et al.Krüppel-like factor 5 mediates the transforming activity of oncogenic H-Ras.Oncogene.2004:23(19):3404-3413.
26. Chen C,Benjamin MS,Sun X,et al.IKLF promotes cell proliferation and tumorigenesis through gene regulation in the TSU-Pr1 human bladder cancer cell line.Int J Cancer,2006,118(6):1346-1355.
27. Chen C,Bhalala HV,Vessella RL,et al.KLF5 is frequently deleted and down-regulated but rarely mutated in prostate cancer.Prostate.2003;55(2):81-88.
28. ChenC,Bhalala HV,QiaoH,et al.A possible tumor suppressor role of the KLF5 transcription factor in human breast cancer.Oncogene.2002;21(43):6567-6572.
29. Yang Y,Goldstein BG, Chao HH, Katz JP.KLF4 and KLF5 regulate proliferation, apoptosis and invasion in esophageal cancer cells. Cancer Biol &Ther,2005, 11 (4):1216-1221.
30.Sun R,Chen X,Yang VW.Intestinal-enriched Krüppel-like factor (Krüppel-like Factor 5) is a positive regulator of cellular proliferation. J Biol Chem,2001,276(10):6897-6900.
1.刘梅冬,刘瑛,刘俊文,等.KLF4过表达对RAW264.7巨噬细胞和C2C12肌原细胞增殖的影响.生命科学研究,2007,11(3):263-267.
2. Kharas MG,Yusuf I,Scarfone VM,et al.KLF 4 suppresses transformation of pre-B cells by ABL oncogenes.Blood,2007,109(2):747-755.
3. Good KL,Tangye SG.Decreased expression of Krüppel-like factors in memory B cells induces the rapid response typical of secondary antibody responses.Proc Natl Acad Sci USA,2007,104(33):13420-13425.
4. Luo AP,Kong JP,Hu GX,et al.Discovery of Ca2+-relevant and differentiation-associated genes down regulated in esophageal squamous cell carcinoma using cDNA microarray.Oncogene,2004,23(6):1291-1299.
5. Wang N,Liu ZH,Xiu FD,et al.Down-regulation of gut-enriched Krüppel-like factor expression in esophageal cancer.World J Gastroenterol,2002,8(6):966-970.
6. Xu J,Lu BJ,Xu FY,et al.Dynamic down-regulation of Krüppel-like factor 4 in colorectal adenoma-carcinoma sequence. Cancer Res Clin Oncol, 2008,134 (8):891-898.
7.房新辉,杨玉秀,韩双印,等.肝癌组织中KLF4的表达及意义.山东医药, 2009,49(1):4-6.
8. Bianchi F,Hu J,Pelosi G,et al.Lung cancers detected by screening with spiral computed tomography have a malignant phenotype when analyzed by cDNA microarray.Clin Cancer Res,2004,10(18 pt 1):6023-6028.
9.刘红,崔竹梅,李玉军,等.子宫内膜癌组织锌指蛋白KLF4的表达及临床意义.山东医药,2005,45(24):29.
10. Luo J,Dunn T,Ewing C,et al.Gene expression signature of benign prostatic hyperplasia revealed by cDNA microarray analysis. Prostate, 2002,51(3):189-200.
11. Ohnishi S,Ohnami S,Laub F,et al.Downregulation and growth inhibitory effect of epithelial-type Krüppel-like transcription factor KLF4, but not KLF5,in bladder cancer.Biochem Biophys Res Commun,2003,308(2):251-256.
12. Zhang L,Wali A,Ramana CV,et al.Cell growth inhibition by okadaic acid involves gut-enriched Krüppel-like factor mediated enhanced expression of c-Myc.Cancer Res,2007,67(21):10198-10206.
13. Chen XM,Whitney EM,Gao SY,et al.Transcriptional profiling of Krüppel-like factor 4 reveals a function in cell cycle regulation and epithelial differentiation.J MolBiol,2003,326(3):665-677.
14. Shields JM,Christy RJ,Yang VW.Identification and characterization of a gene encoding a gut-enriched Krüppel-like factor expressed during growth arrest.J Biol Chem,1996,271(33):20009-20017.
15. Rolland AP. Form genes to gene medicines:recent advances in nonviral gene delivery. Crit Rev Ther Grug Carrier Syst. 1998,15(2):143-198.
16. Spencer SC. Electroporation technique of DNA transfection. Applied Biochemistry and Biotechnology, 1993,42(1):75-82.
17.Walters DK,Jelinek DF.The effectiveness of double-stranded short inhibitory RNAs(siRNAs) may depend on the method of transfection.Antisense Nucleic Acid Drug Dev, 2002,12(6):411-418.
18. Wang D,Jing NH,Lin QS.Strearylamine liposome as a new efficient reagent for DNA transfection of eukaryotic cells.Biochem Biophy Res Commu,1996,226(2):450-455.
19. Gilmore IR,Fox SP,Hollins AJ,et al.Delivery strategies for siRNA-mediated gene silencing.Curr Drug Deliv.2006,3(2):147-155.
20. Byrnes AP,Rusby JE,Wood MJA,et al.Adenovirus gene transfer causes inflammation in the brain. Neuroscience,1995,66(4):1015-1024.
21.Liu CM,Liu DP,Dong WJ,et al.Retrovirus vector-mediated stable gene silencing in human cell.Biochemical and Biophysical Research Communications,2004,313(3): 716-720.
22. Li S,Ma Z. Nonviral gene therapy. Curr Gene Ther,2001,1(2):201-226.
23. Dalby B,Cates S,Harris A,et al.Advanced transfection with lipofectamine 2000 reagent: primary neurons, siRNA, and high-througuput applications.Methods,2004,33(2):95-103.
1. Shields JM,Christy RJ,Yang VW.Identification and characterization of a gene encoding a gut-enriched Kruppel-like factor expressed during growth arrest.J Biol Chem,1996,271(33):20009-20017.
2. Yet SF,McA’Nulty MM,Folta SC,et al.Human EZF,a Krüppel-like zinc finger protein,is expressed in vascular endothelial cells and contains transcriptional activation and repression domains.J Biol Chem,1998,273(2):1026-1031.
3. Ton-That H,Kaestner KH,Shields JM,et al.Expression of the gut-enriched Krüppel-like factor gene during development and intestina1 tumorigenesis.FEBS Lett,1997,419(2-3):239-243.
4.吴晓英,陈卫昌.人胃腺癌组织中KLF4表达及临床意义.苏州医学,2008,31(2):71-75.
5. Kawada K,Yonei T,Ueoka H,et al.Comparison of chemosensitivity tests: clonogenic assay versus MTT assay.Acta Med Okayama,2002,56(3):129-134.
6.韩梅,陈卫昌,严苏.重组人白细胞介素24蛋白的纯化及其对胃癌细胞凋亡的影响.苏州大学学报(医学版),2006,26(3):362-366.
7. Shie JL,Chen ZY,OpBrien MJ,et al.Role of gut-enriched Krüppel-like factor in colonic cell growth and differentiation.Am J Physiol Gastrointest Liver Physiol,2000,279(4):G806～G814.
8.王渝,柯昌庶,赵秋,等.E-cadherin,β-catenin,Cyclin D1在胃腺癌中的表达及临床意义.世界华人消化杂志,2007,15(4): 403-407.
9.王桂兰,陈莉,李杏玉,等.NET21、Ki67和CD34在胃癌组织中的表达及其临床病理意义.肿瘤防治研究,2009,36(3):216-220.
10. Wang N,Liu ZH,Xiu FD,et al.Down-regulation of gut-enriched Krüppel-like factor expression in esophageal cancer.World J Gastroenterol,2002,8(6):966-970.
11. Van Seuningen I,PerraisM,Pigny P,et al.Sequence of the 5′- flanking region and promoter activity of the human mucin gene MUC5B in different phenotypes of colon cancer cells. Biochem J,2000,348 Pt 3:675-686.
12. Miller KA,Eklund EA,Peddinghaus ML,et al.Krüppel-like factor 4 regulates laminin alpha3A expression in mammary epithelial cells.J Biol Chem, 2001, 276(46):42863-42868.
13. Zhang W,Geiman DE,Shields JM,et al.The gutenriched Krüppel-like factor (Krüppel-like factor 4)mediates the transactivating effect of p53 on the p21WAF1/Cip1 promoter.J Biol Chem,2000,275(24):18391-18398.
14. Chen X,Johns DC,Geiman DE,et al.Krüppel-like factor 4(gut-enriched Krüppel-like factor)inhibits cell proliferation by blocking G1/S progression of the cell cycle.J Biol Chem,2001,276(32):30423-30428.
1.吴学文,王邦茂,曹晓沧.hTR反义PS—ODN联合顺铂对人胃癌裸鼠皮下移植瘤作用的体内研究.肿瘤研究与临床,2005,17(4):226-229.
2. Alder DD,Carson PL,Rubin JM,et al.Doppler ultrasound flowimaging in the study of breast canner:Pre-liminary findings.Ultrasound Med Biol,1990,16(6):553-559.
3.郑金锋,曹永成,耿明,等.钙粘素、Ki67和p16在人脑胶质瘤中的表达及意义.中国临床神经外科杂志,2006,11(8):473-475.
4. Birner P,Schindle M,Obermair A,et al.Overexpression of Hypoxia -inducible Factor 1αIs a Marker for an Unfavorable Prognosis in Early -Stage Invasive Cervical Cancer. Cancer Res,2000,60(17):4693-4696.
5. Weidner N.Intratumor microvessel density as a prognostic factor in cancer.Am J Pathol,1995,147(1):9-19.
6.万远廉,戎龙,刘玉树,等.组织因子对大肠癌细胞侵袭及血行转移的影响.中华外科杂志,2005,43(19):1265-1267.
7.肖航,恽时锋,刘年双主编.实验动物科学与应用.南京:凤凰出版传媒集团江苏科学技术出版社,2008,130-137.
8. Xie K,Wei D,Huang S.Transcription anti-angiogenesis therapy of human pancreatic cancer.Cytokine Growth Factor Rev,2006,l7(3):l47-l56.
9. Hicklin DJ, Ellis LM. Role of the vascular endothelial growth factor pathway in tumor growth and angiogenesis Journal clinical oncology, 2005,23(5):1011-1027.
10. Gerber HP, Ferrara N. The role of VEGF in normal and neoplastic hematopoiesis.J Mol Med,2003,81(1):20-31.
11. Vermeulen PB, Colpaert C, Salgado R, et al. Liver metastases from colorectal adenocarcinomas grow in three patterns with different angiogenesis and desmoplasia.J Pathol,2001,195(3):336-342.
12. Ferrara N.Vascular Endothelial Growth Factor as a Target for Anticancer Therapy.Oncologist,2004,9(suppl 1):2-10.
13. Fang J, Shing Y, Wiederschain D, et al.Matrix metalloproteinase-2 is required for the switch to the angiogenic phenotype in a tumor model. PNAS,2000,97(8):3884-3889.
14. Kahashima A,Maehara Y,Kakeji Y,et al.Overexpression of vascular endothelial growth factor C is related to lymphogenous metastasis in early gastric carcinoma. Oncology,2001,60(2):146-150.
15.郑海,陈明,张景辉,等.核转录因子KLF4与VEGF启动子上游DNA序列相互作用研究.华中科技大学学报(医学版),2008,37(6):808-811.
[1] Jane van Vliet,Linda A.Crofts,Kate G R. Quinlan,et al.Human KLF17 is a new member of the Sp/KLF family of transcription factors.J Genomics, 2006,87(4):474-482.
[2] Yet SF,McA’Nulty MM,Folta SC,et al.Human EZF,a Krüppel-like zinc finger protein,is expressed in vascular endothelial cells and contains transcriptional activation and repression domains.J Biol Chem, 1998,273(2):1026-1031.
[3] Jenkins TD,Opitz OG,Okano J,Rustgi AK.Transactivation of the human keratin 4 and Epstein-Barr virus ED-L2 promoters by gut-enriched Krüppel-like factor.J Biol Chem,1998,273(17):10747-10754.
[4] Shie JL,Chen ZY,OpBrien MJ,et al.Role of gut-enriched Krüppel-like factor in colonic cell growth and differentiation.Am J Physiol Gastrointest Liver Physiol, 2000, 279(4): G806～G814.
[5] Shields JM,Christy RJ,Yang VW.Identification and characterization of a gene encoding a gut-enriched Krüppel-like factor expressed during growth arrest.J Biol Chem, 1996, 271(33):20009-20017.
[6] Song A,Patel A,Thamatrakoln K,et al.Functional domains and DNA- binding sequences of RFLAT-1/KLF13, a Krüppel-like transcription factor of activated Tlymphocytes.J Biol Chem,2002,277(33):30055-30065.
[7] Evans PM,Zhang W,Chen X,Yang J,et al.Krüppel-like factor 4 is acetylated by p300 and regulates gene transcription via modulation of histone acetylation .J Biol Chem,2007,282(47):33994-34002.
[8] Shields JM,Yang VW.Two potent nuclear 1ocalization signals in The gut-enriched Krüppel-like factor define a subfamily of closely related Krüppe1 proteins.J Biol Chem,1997,272(29):18504-18507.
[9] Garrett-Sinha LA,Eberspaecher H,Seldin MF, et al.A gene for a novel zinc-finger protein expressed in differentiated epithelial cells and transiently in certain mesenchymal cells.J Biol Chem,1996,271(49): 31384-31390.
[10] Panigada M,Porcellini S,Sutti F,et al.GKLF in thymus epithelium as adevelopmentally regulated element of thymocyte-stroma cross-talk. Mech Dev,1999, 81(1-2):103-113.
[11] Behr R and Kaestner KH. Developmental and cell type-specific expression of the zinc finger transcription factor Krüppel-like factor 4 (Klf4) in postnatal mouse testis.Mech Dev,2002,115(1-2):167-169.
[12] Ohnishi S,Laub F,Matsumoto N,et al.Developmental expression of the mouse gene coding for the Krüppel-like transcription factor KLF4.Dev Dyn, 2000,217 (4):421 -429.
[13] Chiambaretta F,De Graeve F,Turet G,et al.Cell and tissue specific expression of human Krüppel-like transcription factors in human ocular surface.Mol Vis,2004, 10:901-909.
[14] Foster KW,Frost AR,McKie-Bell P,et al.Increase of GKLF messenger RNA and protein expression during progression of breast cancer.Cancer Res,2000, 60(22): 6488-6495.
[15] Hamik A,Lin Z,Kumar A,et al.Krüppel-like factor 4 regulates endothelial inflame -mation.J Biol Chem,2007,282(18):13769-13779.
[16]刘梅冬,刘瑛,刘俊文,等.KLF4过表达对RAW264.7巨噬细胞和C2C12肌原细胞增殖的影响.生命科学研究,2007,11(3):263-267.
[17] Liu JW,Zhang H,Liu Y,et al.KLF4 regulates the expression of interleukin-10 in RAW264.7 macrophages.Biochem Biophys Res Commun,2007, 362(3):575-581.
[18] Liu Y,Zhao J,Liu JW,et al.Up-regulation of the constitutively expressed HSF73 by KLF4. Cell Stress Chaperones,2008,13(3):337-345.
[19] Liu MD,Liu Y,Liu JW,et al.Effect of Krüppel-like factor 4 overexpression on heat stress-induced apoptosis of Raw264.7 macrophages.Zhong Nan Da Xue Xue Bao(Yi Xue Ban),2007,32(6):1002-1006.
[20] Katz JP,Perreault N,Goldstein BG,et al.The zinc-finger transcription factor Klf4 is required for terminal differentiation of goblet cells in the colon. Development, 2002, 129(11):2619-2628.
[21] Segre JA,Bauer C,Fuchs E.Klf4 is a transcription factor required for establishing the barrier function of the skin.Nat Genet,1999, 22(4):356-360.
[22] Swamynathan SK,Katz JP,Kaestner KH,et al.Conditional deletion of mouse Klf4 gene results in corneal epithelial fragility , stromal edema and loss of conjunctival goblet cells.Mol Cell Biol,2007,27(1):182-194.
[23] Luo TH,Zhao Y,Li G,et a1.Differential expression of genes in omental fat of normal weight and obese subjects and obese diabetic patient using cDNA microarray.上海第二医科大学学报(英文版),2007,19(1):1-7,36.
[24]吴铃,赵萸,骆天红,等.转录因子KLF4在脂肪细胞分化过程中的表达变化.上海医学,2007,30(12):930-932.
[25] Kharas MG,Yusuf I,Scarfone VM,et al.KLF 4 suppresses transformation of pre-B cells by ABL oncogenes.Blood,2007,109(2):747-755.
[26] Good KL,Tangye SG.Decreased expression of Kruppel-like factors in memory B cells induces the rapid response typical of secondary antibody responses.Proc Natl Acad Sci USA,2007,104(33):13420-13425.
[27] Wei D,Kanai M,Huang S,et al.Emerging role of KLF4 in Human gastrointestinal cancer.Carcinogenesis,2006,27(1):23-31.
[28] Shie JL,Chen ZY,Fu M,et al.Gut-enriched Krüppel-like factor repressses cyclin D1 promoter activity through Sp1 motif.Nucleic Acids Res,2000,28(15):2969-2976.
[29]王晓颖,朱延波,林晓珠,等.胰腺导管腺癌Spl、PTEN和KLF4的表达及其与微血管密度的关系。诊断学理论与实践,2007,6(5):427-430.
[30] Mahatan CS,Kaestner KH,Geiman DE,et al.Characterization of the structure and regulation of the murine gene encoding gut-enriched Krüppel-like factor(Krüppel-like factor 4).Nucleic Acids Res 1999,27(23):4562-4569.
[31] Wang N,Liu ZH,Ding F,et al.Down-regulation of Gut-enriched Krüppel-like factor expression in esophageal cancer.World J Gastroenterol,2002,8(6):966-970.
[32] Chen ZY,Shie JL,Tseng CC.Up-regulation of gut-enriched krüppel-like factor by interferon-γ,in human colon carcinoma cells.FEBS Lett, 2000,477(1):67-72.
[33] Chen ZY,Shie JL,Tseng CC.STAT1 is required for IFN-gamma-mediated gut- enriched Kruppel-like factor expression.Exp Cell Res,2002, 281(1):19-27.
[34] Zhang W,Geiman DE,Shields JM,et al.The gut-enriched Krüppel-like factor (Krüppel-like factor 4)mediates the transactivating effect of p53 on the p21WAF1/Cip1 promoter.J Biol Chem,2000,275(24):18391-18398.
[35] Brembeck FH,Rustgi AK.The tissue-dependent keratin 19 gene transcription is regulated by GKLF/KLF4 and Sp1.J Biol Chem, 2000,275(36):28230-28239.
[36] Feinberg MW,Wara AK,Cao Z,et al.The Krüppel-like factor KLF4 is a critical regulator of monocyte differentiation.EMBO J,2007, 26(18):4138-4148.
[37] Zhang W,Shields JM,Sogawa K,et al.The gut-enriched Krüppel-like factor suppresses the activity of the CYPIA1 promoter in an Spl-dependent fashion.J Biol Chem, 1998,273(28):17917-17925.
[38] Rowland BD,Bernards R,Peeper DS.The KLF4 tumour suppressor is a transcriptional repressor of p53 that acts as a context-dependent oncogene. Nat Cell Biol, 2005, 7(11):1074-1082.
[39] Katz JP,Perreault N,Goldstein BG,et al. Loss of Klf4 in mice causes altered proliferation and differentiation and precancerous changes in the adult stomach. Gastroenterology,2005,128(4):935-945.
[40] Yoon HS,Yang VW.Requirement of Krüppel-like factor 4 in preventing entry into mitosis following DNA damage.J Biol Chem,2004, 279(6):5035-5041.
[41] Chen XM,Whitney EM,Gao SY,et al.Transcriptional profiling of Krüppel-like factor 4 reveals a function in cell cycle regulation and epithelial differentiation.J Mol Biol,2003,326(3):665-677.
[42] Ton-That H,Kaestner KH,Shields JM,et al.Expression of the gut-enriched Krüppel-like factor gene during development and intestina1 tumorigenesis.FEBS Lett, 1997, 419(2-3):239-243.
[43] Luo AP,Kong JP,Hu GX,et al.Discovery of Ca2+-relevant and differentiation -associated genes down regulated in esophageal squamous cell carcinoma usingcDNA microarray.Oncogene,2004,23(6):1291-1299.
[44] Wang N,Liu ZH,Xiu FD,et al.Down-regulation of gut-enriched Krüppel-like factor expression in esophageal cancer.World J Gastroenterol,2002,8(6):966-970.
[45] Bianchi F,Hu J,Pelosi G,et al.Lung cancers detected by screening with spiral computed tomography have a malignant phenotype when analyzed by cDNA microarray.Clin Cancer Res,2004,10(18 pt 1):6023-6028.
[46] Luo J,Dunn T,Ewing C,et al.Gene expression signature of benign prostatic hyperplasia revealed by cDNA microarray analysis.Prostate, 2002,51(3): 189-200.
[47] Ohnishi S,Ohnami S,Laub F,et al.Downregulation and growth inhibitory effect of epithelial-type Krüppel-like transcription factor KLF4, but not KLF5,in bladder cancer.Biochem Biophys Res Commun,2003,308(2):251-256.
[48] Xu J,Lu BJ,Xu FY,et al.Dynamic down-regulation of Krüppel-like factor 4 in colorectal adenoma-carcinoma sequence. Cancer Res Clin Oncol, 2008, 134 (8):891-898.
[49] Ghaleb AM,McConnell BB,Nandan MO,et al.Haploin sufficiency of Krüppel -like factor 4 promotes adenomatous polyposis coli dependent intestinal tumorigenesis. Cancer Res,2007,67(15):7147-7154.
[50]刘红,崔竹梅,李玉军,等.子宫内膜癌组织锌指蛋白KLF4的表达及临床意义。山东医药,2005,45(24):29.
[51]左艳,胡若磊,左莉,等.胃肠富集Kruppel样因子在人结直肠肿瘤中的表达。安徽医科大学学报,2006,41(2):178-181.
[52]房新辉,杨玉秀,韩双印,等.肝癌组织中KLF4的表达及意义。山东医药,2009,49(1):4-6.
[53] Wei D,Gong W ,Kanai M ,et a1. Drastic down-regulation of Krüppel-like factor 4 expression is critical in human gastric cancer development and progression.Cancer Res,2005,65(7):2746-2754.
[54] Cho YG,Song JH,Kim CJ,et al. Genetic and epigenetic analysis of the KLF4 gene in gastric cancer. APMIS,2007,115(7):802-808.
[55] Zhao W,Hisamuddin IM,Nandan MO,et al.Identification of Krüppel-like factor 4 as a potential tumor suppressor gene in colorectal cancer.Oncogene,2004,23(2):395-402.
[56] Huang CC,Liu Z,Li X,et al.KLF4 and PCNA identify stages of tumor initiation in a conditional model of cutaneous squamous epithelial neoplasia. Cancer Biol Ther,2005,4(12):1401-1408.
[57] Pandya AY,Talley LI,Frost AR,et al.Nuclear localization of KLF 4 is associated with an aggressive phenotype in early stage breast cancer.Clin Cancer Res, 2004, 10(8):2709-2719.
[58] Zhang L,Wali A,Ramana CV,et al.Cell growth inhibition by okadaic acid involves gut-enriched Krüppel-like factor mediated enhanced expression of c-Myc.Cancer Res,2007,67(21):10198-10206.
[1] Nishimura T.Total number of genome alterations in sporadic gastrointestinal cancer inferred from pooled analyses in the literature.Tumour Biol,2008,29(6):343-350.
[2] Wen SF,Xie L,McDonald M,et a1.Development and vaildation of sensitive assays to quantitate gene expression after p53 gene therapy and paclitaxel chemotherapy using in vivo dosing in tumor xenograft models.Cancer Gene Ther,2000,7(11):1469-1480.
[3] Ohashi M,Kanai F,Ueno H,et a1.Adenovirus mediated p53 tumour suppressor gene therapy for human gastric cancer cells in vitro and in vivo.Gut,1999,44(3):366-371.
[4] Huh JJ,Wolf JK,Fightmaster DL,et a1.Transduction of adenovirus-mediated wild-type p53 after radiotherapy in human cervical cancer cells.Gynecol Oncol, 2003, 89(2): 243-250.
[5] Bouvet M,Ellis LM,Nishizaki M,et a1.Adenovirus-mediated wild-type p53 gene transfer down-regulates vascular endothelial growth factor expression and inhibits angiogenesisin human colon cancer.Cancer Res,1998,58(11):2288-2292.
[6] Tamura G.Alterations of tumor suppressor and tumor-related genes in the development and progression of gastric cancer.World J Gastroenterology,2006,12(2):192-198.
[7] Jeong YW,Kim KS,Oh JY,et a1.Exogenous wild-type P16INK4A gene induces delayed cell proliferation and promotes chemosen-sitivity through decreased pRB and increased E2F-l expressions.Int J Mol Med, 2003,12(1):61-65.
[8] Kim R,Emi M,Tanabe K,et a1.Preclinical evaluation of antisence Bcl-2 as a chemosensitizer for patients with gastric carcinoma.Cancer,2004,101(10): 2177-2186.
[9]赵亮,赵家宏,孙凌宇,等.RNA干扰技术沉默Star3基因对胃癌细胞SGC7901生物学行为影响的实验研究.中国肿瘤临床,2008,35(6):348-352.
[10] Wei SJ,Chao Y,Hung YM,et a1.S- and G2-phase cell cycle arrests and apeptosis induced by ganciclovir in murine melanoma cells transduced with herpes simplex virus thymidine kinase.Exp Cell Res,1998,241(1):66-75.
[11] Yoshida K,Kawami H,Yamaguchi Y,et a1.Retrovirallytrailsmitted gene therapy forgastric carcinoma using herpes simplex virus thymidine kinase gene. Cancer, 1995, 75(6):1467-1471.
[12] Wiewrodt R,Amin K,Kiefer M,et a1.Adenovirus-mediated gene transfer of enhanced herpes simplex virus thymidine kinase mutants improves prodrug-mediated tumor cell killing.Cancer Gene Ther,2003,10(5):353-364.
[13] Van Dillen IJ,Mulder NH,Vaalburg W,et a1.Influence of the bystander efect on HSV-tk/GCV gene therapy a review.Curt Gene Ther,2002, 2(3):307-322.
[14] Ueda K,Iwahashi M,Nakamori M,et a1.Carcinoembryonic Antigen-specific suicide gene therapy of cytosine deaminase/5-fluorocytosine enhanced by the cre/loxP system in the orthotopic gastric carcinoma model.Cancer Res,2001,61(16):6158-6162.
[15] Kono K,Takahashi A,Sugai H,et al.Dendritic cells pulsed with HER-2/neu-derived peptides can induce specific T-cell responses in patients with gastric cancer.Clin Cancer Res,2002,8(11):3394-3400.
[16] Kosaka K,Yashiro M,Sakate Y,et a1.CD80 gene therapy for lymph node involvement by gastric carcinoma.Int J Oncol,2004,25(5):1319-l325.
[17] Tanaka H,Yashiro M,Sunami T,et a1.ICAM-2 gene therapy for peritoneal dissemination of scirrhous gastric carcinoma.Clin Cancer Res,2004,10(14): 4885-4892.
[18] Kakeji Y,Maehara Y,Sumiyoshi Y,et a1.Angiogenesls as a target for gastric cancer.Surgery,2002,131(1 Suppl):S48-54.
[19] Sako A,Kitayama J,Koyama H,et a1.Transduction of soluble Flt-1 gene to peritoneal mesothelial cells can efectively suppress peritoneal metastasis of gastric cancer.Cancer Res,2004,64(10):3624-3628.
[20] Stoeltzing O,Mccary MF,Key JS,et a1.Role of hypoxia indueible factor-l alpha in gastric cancer cell growth,angiogenesis and vessel maturation.J Natl Cancer Inst,2004,96(10):946-956.