目的探讨ADAM12L在基底细胞样乳腺癌组织中的蛋白和核酸表达水平,并分析其临床意义。方法应用免疫组化法检测86例基底细胞样乳腺癌组织和20例良性乳腺纤维瘤组织的ADAM12L蛋白表达水平,并进一步采用实时荧光定量PCR方法检测60例基底细...目的探讨ADAM12L在基底细胞样乳腺癌组织中的蛋白和核酸表达水平,并分析其临床意义。方法应用免疫组化法检测86例基底细胞样乳腺癌组织和20例良性乳腺纤维瘤组织的ADAM12L蛋白表达水平,并进一步采用实时荧光定量PCR方法检测60例基底细胞样乳腺癌组织及其配对癌旁组织的ADAM12L m RNA表达量。结果免疫组化染色显示,基底细胞样乳腺癌标本中ADAM12L蛋白阳性表达率(84.9%,73/86)显著高于良性纤维瘤组织样本中ADAM12L蛋白阳性表达率(45%,9/20),P<0.05;淋巴结转移阳性者的ADAM12L阳性率(73.8%,31/42)明显高于无淋巴结转移者(47.8%,21/44),χ~2=5.073,P=0.024;临床分期Ⅲ~Ⅳ者,ADAM12L阳性率(74.5%,41/55)明显高于临床分期Ⅰ~Ⅱ者(35.5%,11/31),χ~2=11.073,P<0.01。real-time PCR检测结果显示ADAM12L在基底细胞样乳腺癌组织中的表达量为2.07±0.95,显著高于配对癌旁组织的表达量(P<0.05)。结论基底细胞样乳腺癌组织的ADAM12L蛋白与核酸表达量均显著高于正常或良性乳腺组织,且与乳腺癌淋巴结转移和临床分期有着密切的联系。ADAM12L可能可以作为新的基底细胞样乳腺癌患者的个体化诊疗靶点。展开更多
African swine fever(ASF)is an infectious transboundary disease of domestic pigs and wild boar and spreading throughout Eurasia.There is no vaccine and treatment available.Complex immune escape strategies of African sw...African swine fever(ASF)is an infectious transboundary disease of domestic pigs and wild boar and spreading throughout Eurasia.There is no vaccine and treatment available.Complex immune escape strategies of African swine fever virus(ASFV)are crucial factors affecting immune prevention and vaccine development.MGF360 genes have been implicated in the modulation of the IFN-Ⅰresponse.The molecular mechanisms contributing to innate immunity are poorly understood.In this study,we demonstrated that ASFV MGF360-12 L(MGF360 families 12 L protein)significantly inhibited the mRNA transcription and promoter activity of IFN-βand NF-κB,accompanied by decreases of IRF3,STING,TBK1,ISG54,ISG56 and AP-1 m RNA transcription.Also,MGF360-12 L might suppress the nuclear localization of p50 and p65 mediated by classical nuclear localization signal(NLS).Additionally,MGF360-12 L could interact with KPNA2,KPNA3,and KPNA4,which interrupted the interaction between p65 and KPNA2,KPNA3,KPNA4.We further found that MGF360-12 L could interfere with the NF-κB nuclear translocation by competitively inhibiting the interaction between NF-κB and nuclear transport proteins.These findings suggested that MGF360-12 L could inhibit the IFN-Ⅰproduction by blocking the interaction of importinαand NF-κB signaling pathway,which might reveal a novel strategy for ASFV to escape the host innate immune response.展开更多
文摘目的探讨ADAM12L在基底细胞样乳腺癌组织中的蛋白和核酸表达水平,并分析其临床意义。方法应用免疫组化法检测86例基底细胞样乳腺癌组织和20例良性乳腺纤维瘤组织的ADAM12L蛋白表达水平,并进一步采用实时荧光定量PCR方法检测60例基底细胞样乳腺癌组织及其配对癌旁组织的ADAM12L m RNA表达量。结果免疫组化染色显示,基底细胞样乳腺癌标本中ADAM12L蛋白阳性表达率(84.9%,73/86)显著高于良性纤维瘤组织样本中ADAM12L蛋白阳性表达率(45%,9/20),P<0.05;淋巴结转移阳性者的ADAM12L阳性率(73.8%,31/42)明显高于无淋巴结转移者(47.8%,21/44),χ~2=5.073,P=0.024;临床分期Ⅲ~Ⅳ者,ADAM12L阳性率(74.5%,41/55)明显高于临床分期Ⅰ~Ⅱ者(35.5%,11/31),χ~2=11.073,P<0.01。real-time PCR检测结果显示ADAM12L在基底细胞样乳腺癌组织中的表达量为2.07±0.95,显著高于配对癌旁组织的表达量(P<0.05)。结论基底细胞样乳腺癌组织的ADAM12L蛋白与核酸表达量均显著高于正常或良性乳腺组织,且与乳腺癌淋巴结转移和临床分期有着密切的联系。ADAM12L可能可以作为新的基底细胞样乳腺癌患者的个体化诊疗靶点。
基金sponsored by National key Research and Development Program(Grant No.2017YFD0502301)National College Students’innovation and entrepreneurship training program(201910504017)。
文摘African swine fever(ASF)is an infectious transboundary disease of domestic pigs and wild boar and spreading throughout Eurasia.There is no vaccine and treatment available.Complex immune escape strategies of African swine fever virus(ASFV)are crucial factors affecting immune prevention and vaccine development.MGF360 genes have been implicated in the modulation of the IFN-Ⅰresponse.The molecular mechanisms contributing to innate immunity are poorly understood.In this study,we demonstrated that ASFV MGF360-12 L(MGF360 families 12 L protein)significantly inhibited the mRNA transcription and promoter activity of IFN-βand NF-κB,accompanied by decreases of IRF3,STING,TBK1,ISG54,ISG56 and AP-1 m RNA transcription.Also,MGF360-12 L might suppress the nuclear localization of p50 and p65 mediated by classical nuclear localization signal(NLS).Additionally,MGF360-12 L could interact with KPNA2,KPNA3,and KPNA4,which interrupted the interaction between p65 and KPNA2,KPNA3,KPNA4.We further found that MGF360-12 L could interfere with the NF-κB nuclear translocation by competitively inhibiting the interaction between NF-κB and nuclear transport proteins.These findings suggested that MGF360-12 L could inhibit the IFN-Ⅰproduction by blocking the interaction of importinαand NF-κB signaling pathway,which might reveal a novel strategy for ASFV to escape the host innate immune response.
