The expressions of HBV X gene and ets-2, IGF-I, c-myc and N-ras were studied in 7 pairs of human primary hepatocellular carcinoma (PHC) and tumor-adjacent tissues, using RNA hybridization and im-munoblot methods. The ...The expressions of HBV X gene and ets-2, IGF-I, c-myc and N-ras were studied in 7 pairs of human primary hepatocellular carcinoma (PHC) and tumor-adjacent tissues, using RNA hybridization and im-munoblot methods. The results showed that specific 17 and 28 kD HBV X gene products (HBxAg) were existed in a portion of PHC and tumor-adjacent tissues. The 17 kD HBxAg was detected in the sera of 3 patients who also had 17 kD HBxAg in their liver tissues. Multiple expressions of oncogenes such as ets-2, c-myc and N-ras were observed in PHC and tumor-adjacent tissues that had HBxAg expressed, indicating HBxAg might function as a transactivator in the course of intracellular proto-oncogene activation. It is also observed that in some tumor-adjacnet tissues the expressions of ets-2, c-myc and N-ras were higher than those in corresponding PHC. The relationship of HBxAg to the expression of est-2, IGF-Ⅱ, c-myc and their possible roles in the carcinogenesis of PHC are discussed.展开更多
The SHP-1 protein encoded by the Ptpn6 gene has been extensively studied in hematopoietic cells in the context of inflammation.A point mutation in this gene(Ptpn6spin)causes spontaneous inflammation in mice,which has ...The SHP-1 protein encoded by the Ptpn6 gene has been extensively studied in hematopoietic cells in the context of inflammation.A point mutation in this gene(Ptpn6spin)causes spontaneous inflammation in mice,which has a striking similarity to neutrophilic dermatoses in humans.Recent findings highlighted the role of signaling adapters and kinases in promoting inflammation in Ptpn6spin mice;however,the underlying transcriptional regulation is poorly understood.Here,we report that SYK is important for driving neutrophil infiltration and initiating wound healing responses in Ptpn6spin mice.Moreover,we found that deletion of the transcription factor Ets2 in myeloid cells ameliorates cutaneous inflammatory disease in Ptpn6spin mice through transcriptional regulation of its target inflammatory genes.Furthermore,Ets-2 drives IL-1α-mediated inflammatory signaling in neutrophils of Ptpn6spin mice.Overall,in addition to its well-known role in driving inflammation in cancer,Ets-2 plays a major role in regulating IL-1α-driven Ptpn6spin-mediated neutrophilic dermatoses.展开更多
目的探讨转录因子ETS2(E-twenty six 2)在结直肠癌组织中的表达情况,分析其与结直肠癌患者临床病理参数之间的关系,并评估其临床预后价值。方法收集新鲜的结直肠癌、癌旁和相应正常组织,以及结直肠癌和癌旁组织的石蜡标本,采用实时荧光...目的探讨转录因子ETS2(E-twenty six 2)在结直肠癌组织中的表达情况,分析其与结直肠癌患者临床病理参数之间的关系,并评估其临床预后价值。方法收集新鲜的结直肠癌、癌旁和相应正常组织,以及结直肠癌和癌旁组织的石蜡标本,采用实时荧光定量PCR法检测组织中ETS2 mRNA的表达,免疫组化检测石蜡切片中ETS2蛋白的表达。结果结直肠癌组织中ETS2mRNA的表达明显高于癌旁组织和正常组织(P<0.001),而癌旁组织和正常组织中的ETS2 mRNA表达量差异无统计学意义(P>0.05)。免疫组化结果显示ETS2在52.07%(63/121)的结直肠癌中表达,而仅在13.04%(6/46)的癌旁组织中表达,两者比较差异有统计学意义(P<0.05)。ETS2表达与肿瘤分化程度、浸润深度、淋巴结转移以及MMR状态有关(P<0.05)。ETS2表达与结直肠癌患者术后无进展生存有关(P<0.001)。采用COX多因素回归分析发现,ETS2表达(HR:0.461,95%CI:0.271~0.683,P=0.003)和浸润深度(HR:0.352,95%CI:0.113~0.769,P=0.015)是结直肠癌患者术后无进展生存的独立预后因子。结论与癌旁组织相比,ETS2在结直肠癌组织中的转录和翻译水平都过表达,ETS2是预测结直肠癌患者术后无进展生存的潜在标记物。展开更多
目的:探讨E26转录因子2(E-twenty six 2,Ets2)对肾癌细胞786-0迁移、侵袭的影响及其机制。方法:设计并合成特异性siRNA下调肾癌细胞系786-0中Ets2的表达;并利用划痕实验及Transwell实验检测其迁移及侵袭能力的变化;通过Western blot检...目的:探讨E26转录因子2(E-twenty six 2,Ets2)对肾癌细胞786-0迁移、侵袭的影响及其机制。方法:设计并合成特异性siRNA下调肾癌细胞系786-0中Ets2的表达;并利用划痕实验及Transwell实验检测其迁移及侵袭能力的变化;通过Western blot检测下调Ets2表达后基质金属蛋白酶2(MMP-2)及MMP-9表达水平变化。结果:siRNA能有效下调肾癌786-0细胞系中Ets2的表达。细胞划痕实验结果显示下调Ets2表达后,细胞迁移能力减弱(P<0.01);Transwell实验中NC组穿膜细胞数为(43.80±3.99)个,而siRNA1组为(23.30±4.24)个(P<0.01),siRNA2组为(24.20±3.29)个(P<0.01),细胞侵袭能力减弱。Ets2-siRNA介导的Ets2基因沉默下调了786-0细胞中MMP-2及MMP-9的表达的同时上调了基质金属蛋白酶组织抑制剂1(TIMP1)和TIMP2的表达。结论:Ets2可通过调节MMPs及TIMPs的表达影响肾癌细胞的迁移及侵袭能力。展开更多
Objective:This study was to observe the levels of Ets2 mRNA expression in leukemia patients and investigate the effect of small interfering RNA(siRNA)targeting Ets2 gene on sensibility of human acute monocytic leukemi...Objective:This study was to observe the levels of Ets2 mRNA expression in leukemia patients and investigate the effect of small interfering RNA(siRNA)targeting Ets2 gene on sensibility of human acute monocytic leukemic cell line SHI-1 cells to etoposide(VP-16).Methods:Ets2 mRNA levels were determined by reverse transcription polymerase chain reaction(RT-PCR).After the transfection of Ets2 siRNA to SHI-1 cells by electroporation method,qRT-PCR was used to detect Ets2 gene expression in these cells;VP-16-induced apoptosis was investigated by Annexin V-FITC/PI.Results:Est2 mRNA was detectable in SHI-cells.The Est2 expression rate was respectively 10%in 5 healthy volunteers,60%in 5 acute lymphocytic leukemia(ALL)patients,73.68%in 19 acute nonlymphocytic leukemia(ANLL)patients and 100%in 4 chronic myeloid leukemia(CML)patients.The expression levels of Ets2 mRNA were significantly higher in leukemia patients compared with healthy volunteers.It also showed that siRNA targeting Ets2 gene resulted in substantial loss of Ets2 mRNA of SHI-1 cells compared to the control groups.Downregulation of Ets2 gene expression increased SHI-1 cells apoptosis and VP-16-induced apoptosis of SHI-1 cells.Conclusion:The high-level expression of Ets2 transcription factor in leukemia cells were connected with proliferation and anti-apoptosis of leukemia cells.SiRNA mediated Ets2 gene silencing induced cell apoptosis and enhanced in vitro sensitivity to chemotherapy(VP-16)of SHI-1 cells.It speculated the high-level expression of Ets2 may actually be an unfavorable determinant of chemotherapy sensitivity in leukemia.展开更多
AIM: To study the expression pattern of ETS2 (erythroblastosisvirus oncogene homolog 2) in human esophageal squamouscell carcinoma (ESCC).METHODS: Reverse transcription polymerase chain reaction(RT-PCR) and Northern b...AIM: To study the expression pattern of ETS2 (erythroblastosisvirus oncogene homolog 2) in human esophageal squamouscell carcinoma (ESCC).METHODS: Reverse transcription polymerase chain reaction(RT-PCR) and Northern blot were performed to examinethe expression level of ETS2 mRNA in 37 pairs of ESCCtissue samples. Western blot and immunohistochemistrywere carried out to check the expression level of ETS2 proteinin 30 pairs of ESCC tissue specimens.RESULTS: RT-PCR and Northern blot analysis showed thatETS2 mRNA upregulated in 75.7 % (28/37) examined ESCCtissues relative to matched normal tissues. From those 37cases, 14 cases were randomly selected to perform Westernblot and the results revealed that ETS2 protein overexpressedin 71.4 % (10/14) checked ESCC tissues compared with thecorresponding normal tissues. Moreover, the expressionpatterns of ETS2 protein in those 14 cases were identical tothose of ETS2 mRNA displayed by RT-PCR or Northern Blot.Immunohistochemistry analysis showed that the expressionlevel of ETS2 protein rose in 75 % (12/16) tumor epithelialcells contrasted to the normal cells. Altogether the expressionlevel of ETS2 protein increased in 73.3 % (22/30) checkedESCC tissue samples contrary to their normal counterparts.CONCLUSION: The results suggested that ETS2overexpressed in paired human ESCC tissue samples at bothmRNA and protein levels and may be associated with thetumorigenesis of esophagus.展开更多
文摘The expressions of HBV X gene and ets-2, IGF-I, c-myc and N-ras were studied in 7 pairs of human primary hepatocellular carcinoma (PHC) and tumor-adjacent tissues, using RNA hybridization and im-munoblot methods. The results showed that specific 17 and 28 kD HBV X gene products (HBxAg) were existed in a portion of PHC and tumor-adjacent tissues. The 17 kD HBxAg was detected in the sera of 3 patients who also had 17 kD HBxAg in their liver tissues. Multiple expressions of oncogenes such as ets-2, c-myc and N-ras were observed in PHC and tumor-adjacent tissues that had HBxAg expressed, indicating HBxAg might function as a transactivator in the course of intracellular proto-oncogene activation. It is also observed that in some tumor-adjacnet tissues the expressions of ets-2, c-myc and N-ras were higher than those in corresponding PHC. The relationship of HBxAg to the expression of est-2, IGF-Ⅱ, c-myc and their possible roles in the carcinogenesis of PHC are discussed.
基金supported by the K22 NIAID Career Transition Award Al 127836 to P.G.,the National Institutes of Health grants CAI 63507,AR056296,Al 124346 and AI101935 and by the American Lebanese Syrian Associated Charities to T.-D.K。
文摘The SHP-1 protein encoded by the Ptpn6 gene has been extensively studied in hematopoietic cells in the context of inflammation.A point mutation in this gene(Ptpn6spin)causes spontaneous inflammation in mice,which has a striking similarity to neutrophilic dermatoses in humans.Recent findings highlighted the role of signaling adapters and kinases in promoting inflammation in Ptpn6spin mice;however,the underlying transcriptional regulation is poorly understood.Here,we report that SYK is important for driving neutrophil infiltration and initiating wound healing responses in Ptpn6spin mice.Moreover,we found that deletion of the transcription factor Ets2 in myeloid cells ameliorates cutaneous inflammatory disease in Ptpn6spin mice through transcriptional regulation of its target inflammatory genes.Furthermore,Ets-2 drives IL-1α-mediated inflammatory signaling in neutrophils of Ptpn6spin mice.Overall,in addition to its well-known role in driving inflammation in cancer,Ets-2 plays a major role in regulating IL-1α-driven Ptpn6spin-mediated neutrophilic dermatoses.
文摘目的探讨转录因子ETS2(E-twenty six 2)在结直肠癌组织中的表达情况,分析其与结直肠癌患者临床病理参数之间的关系,并评估其临床预后价值。方法收集新鲜的结直肠癌、癌旁和相应正常组织,以及结直肠癌和癌旁组织的石蜡标本,采用实时荧光定量PCR法检测组织中ETS2 mRNA的表达,免疫组化检测石蜡切片中ETS2蛋白的表达。结果结直肠癌组织中ETS2mRNA的表达明显高于癌旁组织和正常组织(P<0.001),而癌旁组织和正常组织中的ETS2 mRNA表达量差异无统计学意义(P>0.05)。免疫组化结果显示ETS2在52.07%(63/121)的结直肠癌中表达,而仅在13.04%(6/46)的癌旁组织中表达,两者比较差异有统计学意义(P<0.05)。ETS2表达与肿瘤分化程度、浸润深度、淋巴结转移以及MMR状态有关(P<0.05)。ETS2表达与结直肠癌患者术后无进展生存有关(P<0.001)。采用COX多因素回归分析发现,ETS2表达(HR:0.461,95%CI:0.271~0.683,P=0.003)和浸润深度(HR:0.352,95%CI:0.113~0.769,P=0.015)是结直肠癌患者术后无进展生存的独立预后因子。结论与癌旁组织相比,ETS2在结直肠癌组织中的转录和翻译水平都过表达,ETS2是预测结直肠癌患者术后无进展生存的潜在标记物。
文摘目的:探讨E26转录因子2(E-twenty six 2,Ets2)对肾癌细胞786-0迁移、侵袭的影响及其机制。方法:设计并合成特异性siRNA下调肾癌细胞系786-0中Ets2的表达;并利用划痕实验及Transwell实验检测其迁移及侵袭能力的变化;通过Western blot检测下调Ets2表达后基质金属蛋白酶2(MMP-2)及MMP-9表达水平变化。结果:siRNA能有效下调肾癌786-0细胞系中Ets2的表达。细胞划痕实验结果显示下调Ets2表达后,细胞迁移能力减弱(P<0.01);Transwell实验中NC组穿膜细胞数为(43.80±3.99)个,而siRNA1组为(23.30±4.24)个(P<0.01),siRNA2组为(24.20±3.29)个(P<0.01),细胞侵袭能力减弱。Ets2-siRNA介导的Ets2基因沉默下调了786-0细胞中MMP-2及MMP-9的表达的同时上调了基质金属蛋白酶组织抑制剂1(TIMP1)和TIMP2的表达。结论:Ets2可通过调节MMPs及TIMPs的表达影响肾癌细胞的迁移及侵袭能力。
基金Supported by a grant from the Natural Science Foundation of Hubei Province(No.2009CDB416)
文摘Objective:This study was to observe the levels of Ets2 mRNA expression in leukemia patients and investigate the effect of small interfering RNA(siRNA)targeting Ets2 gene on sensibility of human acute monocytic leukemic cell line SHI-1 cells to etoposide(VP-16).Methods:Ets2 mRNA levels were determined by reverse transcription polymerase chain reaction(RT-PCR).After the transfection of Ets2 siRNA to SHI-1 cells by electroporation method,qRT-PCR was used to detect Ets2 gene expression in these cells;VP-16-induced apoptosis was investigated by Annexin V-FITC/PI.Results:Est2 mRNA was detectable in SHI-cells.The Est2 expression rate was respectively 10%in 5 healthy volunteers,60%in 5 acute lymphocytic leukemia(ALL)patients,73.68%in 19 acute nonlymphocytic leukemia(ANLL)patients and 100%in 4 chronic myeloid leukemia(CML)patients.The expression levels of Ets2 mRNA were significantly higher in leukemia patients compared with healthy volunteers.It also showed that siRNA targeting Ets2 gene resulted in substantial loss of Ets2 mRNA of SHI-1 cells compared to the control groups.Downregulation of Ets2 gene expression increased SHI-1 cells apoptosis and VP-16-induced apoptosis of SHI-1 cells.Conclusion:The high-level expression of Ets2 transcription factor in leukemia cells were connected with proliferation and anti-apoptosis of leukemia cells.SiRNA mediated Ets2 gene silencing induced cell apoptosis and enhanced in vitro sensitivity to chemotherapy(VP-16)of SHI-1 cells.It speculated the high-level expression of Ets2 may actually be an unfavorable determinant of chemotherapy sensitivity in leukemia.
基金China key program on basic research,No. G1998051021The Chinese Hi-tech R&D program(2001AA231041)National Natural Science Foundation of China,No.39993402
文摘AIM: To study the expression pattern of ETS2 (erythroblastosisvirus oncogene homolog 2) in human esophageal squamouscell carcinoma (ESCC).METHODS: Reverse transcription polymerase chain reaction(RT-PCR) and Northern blot were performed to examinethe expression level of ETS2 mRNA in 37 pairs of ESCCtissue samples. Western blot and immunohistochemistrywere carried out to check the expression level of ETS2 proteinin 30 pairs of ESCC tissue specimens.RESULTS: RT-PCR and Northern blot analysis showed thatETS2 mRNA upregulated in 75.7 % (28/37) examined ESCCtissues relative to matched normal tissues. From those 37cases, 14 cases were randomly selected to perform Westernblot and the results revealed that ETS2 protein overexpressedin 71.4 % (10/14) checked ESCC tissues compared with thecorresponding normal tissues. Moreover, the expressionpatterns of ETS2 protein in those 14 cases were identical tothose of ETS2 mRNA displayed by RT-PCR or Northern Blot.Immunohistochemistry analysis showed that the expressionlevel of ETS2 protein rose in 75 % (12/16) tumor epithelialcells contrasted to the normal cells. Altogether the expressionlevel of ETS2 protein increased in 73.3 % (22/30) checkedESCC tissue samples contrary to their normal counterparts.CONCLUSION: The results suggested that ETS2overexpressed in paired human ESCC tissue samples at bothmRNA and protein levels and may be associated with thetumorigenesis of esophagus.
