BACKGROUND NIMA related kinase 2(NEK2) is closely related to mitosis, and it is currently considered to be over-expressed frequently in many poorly prognostic cancers.However, the effect of the up-regulated NEK2 on ce...BACKGROUND NIMA related kinase 2(NEK2) is closely related to mitosis, and it is currently considered to be over-expressed frequently in many poorly prognostic cancers.However, the effect of the up-regulated NEK2 on cellular signaling in tumors,such as gastric cancer(GC), is con-fusing.AIM To determine the role of the up-regulation of NEK2 in GC.METHODS To investigate the pathological significance of NEK2 in GC, the expression pattern of NEK2 in GC was investigated based on the 'Oncomain' database and compared between 30 pairs of cancer samples and adjacent tissues. The coexpression of NEK2 and ERK in GC was analyzed using The Cancer Genome Atlas(TCGA) database and confirmed in clinical samples by quantitative realtime PCR(qRT-PCR), and the survival curve was also plotted. Western blot or qRT-PCR was used to analyze the effect of NEK2 on the phosphorylation levels of ERK and c-JUN in two GC cell lines(BGC823 and SGC7901) with NEK2 overexpression, and the expression of the downstream effector cyclin D1.Furthermore, CCK8, EdU incorporation assay, and flow cytometry were used to detect the proliferative ability of BGC823 and SGC7901 cells with stably silenced ERK.RESULTS NEK2 was significantly up-regulated in human GC tissues. ERK was significantly associated with NEK2 expression in human clinical specimens, and combined overexpression of NEK2 and ERK potentially forecasted a poor prognosis andsurvival in GC patients. NEK2 knockdown in GC cells inhibited ERK and c-JUN phosphory-lation and reduced the transcription of cyclin D1. More interestingly,NEK2 can rescue the inhibition of cellular viability, proliferation, and cell cycle progression due to ERK knockdown.CONCLUSION Our results indicate that NEK2 plays a carcinogenic role in the malignant proliferation of GC cells via the ERK/MAPK signaling, which may be important for treatment and improving patient survival.展开更多
Ras protein signaling pathways are important in controlling the plight of diferent types of cancer. Here we discussed the paper entitled "Small molecule stabilization of the KSR inactive state antagonizes oncogen...Ras protein signaling pathways are important in controlling the plight of diferent types of cancer. Here we discussed the paper entitled "Small molecule stabilization of the KSR inactive state antagonizes oncogenic Ras signalling" published in Nature journal on inactivating the kinase suppressor of Ras(KSR) protein using a small molecule as an inhibitor by Dhawan et al. A biphenyl ether analogue of a quinazoline binds in one of the binding pockets of KSR and results in stabilization of its inactive state. In this inactive state, KSR is unable to take part in the cascade of protein association to perform the signalling process.展开更多
目的探讨南方红豆杉水提物通过抑制Ras/MAPK信号通路相关靶点蛋白表达,调控裸鼠HER2阳性胃癌移植瘤生长及其机制。方法建立荷瘤裸鼠模型,将80只BALB/c裸鼠接种人表皮生长因子-2(HER2)阳性胃癌NCI-N87细胞株,并随机分组给药及取瘤,采用We...目的探讨南方红豆杉水提物通过抑制Ras/MAPK信号通路相关靶点蛋白表达,调控裸鼠HER2阳性胃癌移植瘤生长及其机制。方法建立荷瘤裸鼠模型,将80只BALB/c裸鼠接种人表皮生长因子-2(HER2)阳性胃癌NCI-N87细胞株,并随机分组给药及取瘤,采用Western Blot检测HER2、KRAS蛋白表达,RT-PCR定量检测HER2、KRAS m RNA表达水平。结果 1Western blot检测HER2、KRAS蛋白:与空白组比较,各给药组HER2、KRAS蛋白表达不同程度下调[HER2:(1.238±0.123、1.180±0.152、1.159±0.087、0.876±0.098、0.651±0.108、0.554±0.110)比(1.482±0.101),P<0.05或P<0.01;KRAS:(0.768±0.040、0.680±0.019、0.821±0.170、0.716±0.023、0.630±0.049、0.739±0.044)比(1.015±0.033),P均<0.05];与赫赛汀组比较,中剂量联合组KRAS蛋白表达显著下调(0.630±0.049比0.759±0.029,P<0.05);2RT-PCR检测HER2、KRAS m RNA表达:与空白组比较,各给药组HER2、KRAS m RNA表达不同程度下调[HER2 m RNA:(0.916±0.026、0.783±0.061、0.846±0.021、0.741±0.079、0.660±0.079、0.673±0.045)比(1.000±0.193),P均<0.05;KRAS m RNA:(0.643±0.065、0.551±0.173、0.572±0.267、0.329±0.250、0.036±0.007、0.351±0.257)比(1.001±0.132),P<0.05或P<0.01];与赫赛汀组比较,中剂量联合组KRAS m RNA表达显著下调(0.036±0.007比0.362±0.162,P<0.01)。结论南方红豆杉水提物可通过Ras/MAPK信号通路部分下调HER2、KRAS蛋白及其m RNA表达水平,联合赫赛汀可增强其抑制作用。展开更多
文摘BACKGROUND NIMA related kinase 2(NEK2) is closely related to mitosis, and it is currently considered to be over-expressed frequently in many poorly prognostic cancers.However, the effect of the up-regulated NEK2 on cellular signaling in tumors,such as gastric cancer(GC), is con-fusing.AIM To determine the role of the up-regulation of NEK2 in GC.METHODS To investigate the pathological significance of NEK2 in GC, the expression pattern of NEK2 in GC was investigated based on the 'Oncomain' database and compared between 30 pairs of cancer samples and adjacent tissues. The coexpression of NEK2 and ERK in GC was analyzed using The Cancer Genome Atlas(TCGA) database and confirmed in clinical samples by quantitative realtime PCR(qRT-PCR), and the survival curve was also plotted. Western blot or qRT-PCR was used to analyze the effect of NEK2 on the phosphorylation levels of ERK and c-JUN in two GC cell lines(BGC823 and SGC7901) with NEK2 overexpression, and the expression of the downstream effector cyclin D1.Furthermore, CCK8, EdU incorporation assay, and flow cytometry were used to detect the proliferative ability of BGC823 and SGC7901 cells with stably silenced ERK.RESULTS NEK2 was significantly up-regulated in human GC tissues. ERK was significantly associated with NEK2 expression in human clinical specimens, and combined overexpression of NEK2 and ERK potentially forecasted a poor prognosis andsurvival in GC patients. NEK2 knockdown in GC cells inhibited ERK and c-JUN phosphory-lation and reduced the transcription of cyclin D1. More interestingly,NEK2 can rescue the inhibition of cellular viability, proliferation, and cell cycle progression due to ERK knockdown.CONCLUSION Our results indicate that NEK2 plays a carcinogenic role in the malignant proliferation of GC cells via the ERK/MAPK signaling, which may be important for treatment and improving patient survival.
文摘Ras protein signaling pathways are important in controlling the plight of diferent types of cancer. Here we discussed the paper entitled "Small molecule stabilization of the KSR inactive state antagonizes oncogenic Ras signalling" published in Nature journal on inactivating the kinase suppressor of Ras(KSR) protein using a small molecule as an inhibitor by Dhawan et al. A biphenyl ether analogue of a quinazoline binds in one of the binding pockets of KSR and results in stabilization of its inactive state. In this inactive state, KSR is unable to take part in the cascade of protein association to perform the signalling process.
文摘目的探讨南方红豆杉水提物通过抑制Ras/MAPK信号通路相关靶点蛋白表达,调控裸鼠HER2阳性胃癌移植瘤生长及其机制。方法建立荷瘤裸鼠模型,将80只BALB/c裸鼠接种人表皮生长因子-2(HER2)阳性胃癌NCI-N87细胞株,并随机分组给药及取瘤,采用Western Blot检测HER2、KRAS蛋白表达,RT-PCR定量检测HER2、KRAS m RNA表达水平。结果 1Western blot检测HER2、KRAS蛋白:与空白组比较,各给药组HER2、KRAS蛋白表达不同程度下调[HER2:(1.238±0.123、1.180±0.152、1.159±0.087、0.876±0.098、0.651±0.108、0.554±0.110)比(1.482±0.101),P<0.05或P<0.01;KRAS:(0.768±0.040、0.680±0.019、0.821±0.170、0.716±0.023、0.630±0.049、0.739±0.044)比(1.015±0.033),P均<0.05];与赫赛汀组比较,中剂量联合组KRAS蛋白表达显著下调(0.630±0.049比0.759±0.029,P<0.05);2RT-PCR检测HER2、KRAS m RNA表达:与空白组比较,各给药组HER2、KRAS m RNA表达不同程度下调[HER2 m RNA:(0.916±0.026、0.783±0.061、0.846±0.021、0.741±0.079、0.660±0.079、0.673±0.045)比(1.000±0.193),P均<0.05;KRAS m RNA:(0.643±0.065、0.551±0.173、0.572±0.267、0.329±0.250、0.036±0.007、0.351±0.257)比(1.001±0.132),P<0.05或P<0.01];与赫赛汀组比较,中剂量联合组KRAS m RNA表达显著下调(0.036±0.007比0.362±0.162,P<0.01)。结论南方红豆杉水提物可通过Ras/MAPK信号通路部分下调HER2、KRAS蛋白及其m RNA表达水平,联合赫赛汀可增强其抑制作用。
