研究Notch-1信号通路中Notch-1、NICD、Hes1、c-Myc与人甲状腺乳头状癌的关系,探讨Notch-1信号通路在甲状腺乳头状癌中的分子机制。对照人甲状腺乳头状癌及正常甲状腺组织标本各35例,采用Real Time PCR检测Notch-1、Hes1、c-Myc的mRNA...研究Notch-1信号通路中Notch-1、NICD、Hes1、c-Myc与人甲状腺乳头状癌的关系,探讨Notch-1信号通路在甲状腺乳头状癌中的分子机制。对照人甲状腺乳头状癌及正常甲状腺组织标本各35例,采用Real Time PCR检测Notch-1、Hes1、c-Myc的mRNA表达情况,采用免疫组织化学、Western blot方法检测组织标本中Notch-1、NICD、Hes1、c-Myc蛋白的表达情况。Notch-1、Hes1在甲状腺乳头状癌中的mRNA表达水平明显降低,c-Myc mRNA的表达在甲状腺乳头状癌中升高,Notch-1、NICD、Hes1蛋白在人甲状腺乳头状癌中的表达低于正常甲状腺组织(P<0.05),c-Myc蛋白在甲状腺乳头状癌中的表达高于正常甲状腺组织(P<0.05)。甲状腺乳头状癌组织标本中,Notch-1信号通路中Notch-1、NICD、Hes1在基因转录和蛋白质表达水平上均明显下调,而c-Myc的基因转录和蛋白质表达水平均升高,提示Notch-1信号通路在甲状腺乳头状癌的发生发展中起抑癌作用,c-Myc基因表达升高与Notch-1信号通路可能无关。展开更多
RBPjk-dependent Notch signaling regulates both the onset of chondrocyte hypertrophy and the progression to terminal chondrocyte maturation during endochondral ossification. It has been suggested that Notch signaling c...RBPjk-dependent Notch signaling regulates both the onset of chondrocyte hypertrophy and the progression to terminal chondrocyte maturation during endochondral ossification. It has been suggested that Notch signaling can regulate Sox9 transcription, although how this occurs at the molecular level in chondrocytes and whether this transcriptional regulation mediates Notch control of chondrocyte hypertrophy and cartilage development is unknown or controversial. Here we have provided conclusive genetic evidence linking RBPjk-dependent Notch signaling to the regulation of Sox9 expression and chondrocyte hypertrophy by examining tissuespecific Rbpjk mutant（Prx1Cre;Rbpjkf/f）, Rbpjk mutant/Sox9 haploinsufficient（Prx1Cre;Rbpjkf/f;Sox9f/1）,and control embryos for alterations in SOX9 expression and chondrocyte hypertrophy during cartilage development. These studies demonstrate that Notch signaling regulates the onset of chondrocyte maturation in a SOX9-dependent manner, while Notch-mediated regulation of terminal chondrocyte maturation likely functions independently of SOX9. Furthermore, our in vitro molecular analyses of the Sox9 promoter and Notch-mediated regulation of Sox9 gene expression in chondrogenic cells identified the ability of Notch to induce Sox9 expression directly in the acute setting, but suppresses Sox9 transcription with prolonged Notch signaling that requires protein synthesis of secondary effectors.展开更多
文摘研究Notch-1信号通路中Notch-1、NICD、Hes1、c-Myc与人甲状腺乳头状癌的关系,探讨Notch-1信号通路在甲状腺乳头状癌中的分子机制。对照人甲状腺乳头状癌及正常甲状腺组织标本各35例,采用Real Time PCR检测Notch-1、Hes1、c-Myc的mRNA表达情况,采用免疫组织化学、Western blot方法检测组织标本中Notch-1、NICD、Hes1、c-Myc蛋白的表达情况。Notch-1、Hes1在甲状腺乳头状癌中的mRNA表达水平明显降低,c-Myc mRNA的表达在甲状腺乳头状癌中升高,Notch-1、NICD、Hes1蛋白在人甲状腺乳头状癌中的表达低于正常甲状腺组织(P<0.05),c-Myc蛋白在甲状腺乳头状癌中的表达高于正常甲状腺组织(P<0.05)。甲状腺乳头状癌组织标本中,Notch-1信号通路中Notch-1、NICD、Hes1在基因转录和蛋白质表达水平上均明显下调,而c-Myc的基因转录和蛋白质表达水平均升高,提示Notch-1信号通路在甲状腺乳头状癌的发生发展中起抑癌作用,c-Myc基因表达升高与Notch-1信号通路可能无关。
基金supported in part by the following United States National Institute of Health grants: R01 grants (AR057022 and AR063071), R21 grant (AR059733 to MJH), a P30 Core Center grant (AR061307), and a T32 training grant that supported both AK and TPR (AR053459 to Regis J.O’Keefe and Michael J.Zuscik)
文摘RBPjk-dependent Notch signaling regulates both the onset of chondrocyte hypertrophy and the progression to terminal chondrocyte maturation during endochondral ossification. It has been suggested that Notch signaling can regulate Sox9 transcription, although how this occurs at the molecular level in chondrocytes and whether this transcriptional regulation mediates Notch control of chondrocyte hypertrophy and cartilage development is unknown or controversial. Here we have provided conclusive genetic evidence linking RBPjk-dependent Notch signaling to the regulation of Sox9 expression and chondrocyte hypertrophy by examining tissuespecific Rbpjk mutant（Prx1Cre;Rbpjkf/f）, Rbpjk mutant/Sox9 haploinsufficient（Prx1Cre;Rbpjkf/f;Sox9f/1）,and control embryos for alterations in SOX9 expression and chondrocyte hypertrophy during cartilage development. These studies demonstrate that Notch signaling regulates the onset of chondrocyte maturation in a SOX9-dependent manner, while Notch-mediated regulation of terminal chondrocyte maturation likely functions independently of SOX9. Furthermore, our in vitro molecular analyses of the Sox9 promoter and Notch-mediated regulation of Sox9 gene expression in chondrogenic cells identified the ability of Notch to induce Sox9 expression directly in the acute setting, but suppresses Sox9 transcription with prolonged Notch signaling that requires protein synthesis of secondary effectors.
文摘目的研究Notch信号通路在脊髓损伤部位高表达后,对内源性脊髓神经干细胞再生能力的影响,探讨其在脊髓损伤修复中的作用。方法构建鼠NICD(Notch intracellular domain,NICD)质粒,用经典的氧化还原法将NICD质粒结合至葡聚糖磁性纳米颗粒(dextran magnetic nanoparticles,DMN)上,参照Alivisatos和Conwell方法构建纳米化目的基因,在外磁场作用下转染体外培养鼠脊髓神经干细胞,检测转染前后细胞增殖与凋亡情况。结果纳米化NICD-DMN转染体外培养内源性脊髓神经干细胞后,细胞明显增多,而凋亡明显减少,统计学有显著意义(P<0.05)。结论特异性磁性NICD在外磁场协助下明显促进内源性脊髓干细胞增殖,抑制其凋亡。
