目的:探讨解整合素金属蛋白酶17(a disintegrin and metalloproteinase-17,ADAM17)在人胰腺癌细胞株中的表达及其对细胞增殖迁移的影响。方法:利用实时定量PCR法和蛋白质印迹法检测3种人胰腺癌细胞株内ADAM17mRNA和蛋白的表达水平。构...目的:探讨解整合素金属蛋白酶17(a disintegrin and metalloproteinase-17,ADAM17)在人胰腺癌细胞株中的表达及其对细胞增殖迁移的影响。方法:利用实时定量PCR法和蛋白质印迹法检测3种人胰腺癌细胞株内ADAM17mRNA和蛋白的表达水平。构建可诱导表达ADAM17-shRNA的慢病毒载体,转染人胰腺癌细胞株,并筛选出稳定转染的克隆细胞株。在不同浓度(0,30μg/m L)的多西环素诱导ADAM17-shRNA表达后,通过CCK-8法和细胞划痕实验检测人胰腺癌细胞的体外增殖、迁移能力。结果:ADAM17 mRNA及蛋白在人胰腺癌细胞株PANC1、SW1990和Patu8988中均有表达。与未诱导表达ADAM17-shRNA的对照组相比,诱导表达特异性ADAM17-shRNA后,细胞ADAM17蛋白表达和体外增殖、迁移能力均受到明显抑制(均P<0.05)。结论:ADAM17在人胰腺癌细胞中高表达,在其增殖、迁移过程中可能发挥重要作用。展开更多
去整合素-金属蛋白酶17(a disintegrin and metalloproteinase 17,ADAM17)即肿瘤坏死因子α转换酶,在哺乳动物细胞中广泛分布,与细胞黏附、细胞迁移、白细胞募集、蛋白水解等功能密切相关.ADAM17在恶性肿瘤发生发展中起重要作用,一方面...去整合素-金属蛋白酶17(a disintegrin and metalloproteinase 17,ADAM17)即肿瘤坏死因子α转换酶,在哺乳动物细胞中广泛分布,与细胞黏附、细胞迁移、白细胞募集、蛋白水解等功能密切相关.ADAM17在恶性肿瘤发生发展中起重要作用,一方面通过介导膜蛋白脱落激活信号通路,参与细胞增殖、血管生成等;另一方面,通过降解细胞基底膜和细胞外基质,在肿瘤的侵袭和转移中发挥重要作用.因此,ADAM17可能作为肿瘤治疗的潜在靶点,本文就ADAM17在消化系统恶性肿瘤中的相关研究进行综述.展开更多
目的:探讨去整合素-金属蛋白酶17(A disintegrin and metalloproteinase 17,ADAM17)蛋白在食管鳞癌中的表达及其与淋巴结转移的相关性。方法:采用免疫组化SP法检测80例食管鳞癌及对应的正常食管黏膜中ADAM17蛋白的表达水平。采用χ2检验...目的:探讨去整合素-金属蛋白酶17(A disintegrin and metalloproteinase 17,ADAM17)蛋白在食管鳞癌中的表达及其与淋巴结转移的相关性。方法:采用免疫组化SP法检测80例食管鳞癌及对应的正常食管黏膜中ADAM17蛋白的表达水平。采用χ2检验、Pearson相关分析进行统计学处理。结果:食管鳞癌及其切缘的正常食管粘膜中ADAM17蛋白表达阳性率分别为66.25%和6.25%,差异有统计学意义(P<0.05)。食管鳞癌中ADAM17蛋白表达阳性率与淋巴结转移呈正相关(P<0.05)。结论:ADAM17蛋白在食管鳞癌中高表达,在食管鳞癌的发生、侵袭转移中起重要作用。展开更多
Objective To investigate the main proteinases responsible for CD16b shedding under different stimulators. Methods HEK293 cell line stably expressing CD16b was constructed by lentivirus system. The cell line was then ...Objective To investigate the main proteinases responsible for CD16b shedding under different stimulators. Methods HEK293 cell line stably expressing CD16b was constructed by lentivirus system. The cell line was then overexpressed with a disintegrin and metalloproteinase 10 （ADAM10） or ADAM17, sup- pressed with short hairpin RNA of ADAM10 or ADAM I 7, and reconstituted with ADAM 10 or ADAM17, respectively. After each treatment, the cell line was stimulated with ionomycin or phorbol 12-myristate- 13-acetate （PMA） for 12 hours. The soluble CD 16b released from cell membrane was detected by immuno- precipition and immunoblot. Quantitation was then implemented to compare the amount of soluble CD 16b in cell supernatant after stimulation. Results HEK293 cell line stably expressing CD16b was successfully established. When CDI6b ex- pressing cell line was overexpressed with ADAM 10, shedding of CD 16b was increased after stimulation with ionomycin but not PMA; when the cell line overexpressed with ADAM I7, shedding of CDI6b was increased after stimulation with PMA but not ionomycin. Similarly, when ADAM10 was suppressed by short hairpin RNA, CD 16b shedding was decreased after stimulation with ionomycin; when ADAM 17 was suppressed by short hairpin RNA, CD16b shedding was decreased after stimulation with PMA. The shedding of CD16b was increased again when CD16b expressing cell line was reconstituted with ADAM10 and stimulated by ionomycin or reconstituted with ADAM 17 and stimulated by PMA. Conclusions Both ADAM10 and ADAM17 could shed CD16b, but they possess differed prefer- ences. ADAM10 is the main sheddase under stimulation of ionomycin, while ADAM17 is the main sheddase under stimulation of PMA.展开更多
文摘去整合素-金属蛋白酶17(a disintegrin and metalloproteinase 17,ADAM17)即肿瘤坏死因子α转换酶,在哺乳动物细胞中广泛分布,与细胞黏附、细胞迁移、白细胞募集、蛋白水解等功能密切相关.ADAM17在恶性肿瘤发生发展中起重要作用,一方面通过介导膜蛋白脱落激活信号通路,参与细胞增殖、血管生成等;另一方面,通过降解细胞基底膜和细胞外基质,在肿瘤的侵袭和转移中发挥重要作用.因此,ADAM17可能作为肿瘤治疗的潜在靶点,本文就ADAM17在消化系统恶性肿瘤中的相关研究进行综述.
文摘目的:探讨去整合素-金属蛋白酶17(A disintegrin and metalloproteinase 17,ADAM17)蛋白在食管鳞癌中的表达及其与淋巴结转移的相关性。方法:采用免疫组化SP法检测80例食管鳞癌及对应的正常食管黏膜中ADAM17蛋白的表达水平。采用χ2检验、Pearson相关分析进行统计学处理。结果:食管鳞癌及其切缘的正常食管粘膜中ADAM17蛋白表达阳性率分别为66.25%和6.25%,差异有统计学意义(P<0.05)。食管鳞癌中ADAM17蛋白表达阳性率与淋巴结转移呈正相关(P<0.05)。结论:ADAM17蛋白在食管鳞癌中高表达,在食管鳞癌的发生、侵袭转移中起重要作用。
基金Supported by the National Natural Science Foundation of China (30872287)
文摘Objective To investigate the main proteinases responsible for CD16b shedding under different stimulators. Methods HEK293 cell line stably expressing CD16b was constructed by lentivirus system. The cell line was then overexpressed with a disintegrin and metalloproteinase 10 （ADAM10） or ADAM17, sup- pressed with short hairpin RNA of ADAM10 or ADAM I 7, and reconstituted with ADAM 10 or ADAM17, respectively. After each treatment, the cell line was stimulated with ionomycin or phorbol 12-myristate- 13-acetate （PMA） for 12 hours. The soluble CD 16b released from cell membrane was detected by immuno- precipition and immunoblot. Quantitation was then implemented to compare the amount of soluble CD 16b in cell supernatant after stimulation. Results HEK293 cell line stably expressing CD16b was successfully established. When CDI6b ex- pressing cell line was overexpressed with ADAM 10, shedding of CD 16b was increased after stimulation with ionomycin but not PMA; when the cell line overexpressed with ADAM I7, shedding of CDI6b was increased after stimulation with PMA but not ionomycin. Similarly, when ADAM10 was suppressed by short hairpin RNA, CD 16b shedding was decreased after stimulation with ionomycin; when ADAM 17 was suppressed by short hairpin RNA, CD16b shedding was decreased after stimulation with PMA. The shedding of CD16b was increased again when CD16b expressing cell line was reconstituted with ADAM10 and stimulated by ionomycin or reconstituted with ADAM 17 and stimulated by PMA. Conclusions Both ADAM10 and ADAM17 could shed CD16b, but they possess differed prefer- ences. ADAM10 is the main sheddase under stimulation of ionomycin, while ADAM17 is the main sheddase under stimulation of PMA.
