Objective： Impaired signal transduction is associated with tumorigenesis and progression of various kinds of human cancers. Transforming growth factor （TGF）-beta/Smad and ras-mitogen activated protein kinase （MAPK...Objective： Impaired signal transduction is associated with tumorigenesis and progression of various kinds of human cancers. Transforming growth factor （TGF）-beta/Smad and ras-mitogen activated protein kinase （MAPK） are two major signal transduction pathways for adjusting cell proliferation and differentiation. Little is known about TGF-beta/Smad4 in non-small cell lung cancer （NSCLC）. Hereby, we investigated the expression of Smad4 in NSCLC, its correlation with MAPK proteins （including p38, ERK1 and JNK1 proteins） and their clinical significance in NSCLC. Methods： The expressions of Smad4, p38, ERK1 and JNK1 were detected at protein level with Western blotting and immunohistochemistry, at transcription level with RT-PCR. Statistical analysis was performed for the comparisons of expressions of Smad4, p38, ERK1 and JNK1, and their correlation with various clinicopathological parameters and the prognosis of NSCLC. Results： The levels of protein and mRNA expression of Smad4 in lung cancer tissues were significantly lower than in normal tissues （P〈0.05）. All these four proteins were associated with TNM staging. There was a strongly negative correlation between p38 and Smad4. Expressions of Smad4, p38 and JNK1, as well as tumor differentiation and staging were significantly correlated with the prognosis of NSCLC by univariate analysis. By multivariate analysis, only Smad4, p38, tumor differentiation and staging were correlated with the prognosis. Taken together, the negative expression of p38 and positive expression of Smad4 were associated with a better prognosis of NSCLC. Conclusion： Smad4 could be of vital importance for the initiation and development of NSCLC. The expression of Smad4 might be inhibited by p38, supporting a cross-talk between main proteins of TGF-beta/Smad and ras-MAPK signal transduction pathways. Smad4 and p38 could be possible prognostic factors for NSCLC.展开更多
目的观察糖尿病大鼠肾组织中骨形成蛋白7(BMP-7)的表达及探讨其在糖尿病肾病中的可能作用。方法将大鼠分为糖尿病组及正常对照组,分别在第30、60、90、120、150及180 d测定各组的血糖、Ser、24 h尿白蛋白、尿肌酐(Ucr)水平。以HE、PASM...目的观察糖尿病大鼠肾组织中骨形成蛋白7(BMP-7)的表达及探讨其在糖尿病肾病中的可能作用。方法将大鼠分为糖尿病组及正常对照组,分别在第30、60、90、120、150及180 d测定各组的血糖、Ser、24 h尿白蛋白、尿肌酐(Ucr)水平。以HE、PASM染色及ColⅣ蛋白表达衡量肾脏病理改变。用免疫组化及RT-PCR方法检测肾组织中BMP-7、TGF-β1的蛋白及mRNA表达水平。结果糖尿病组各时间点血糖、尿白蛋白量(24 h)均明显高于对照组(P<0．01)。糖尿病组伴随病理改变的加重和ColⅣ表达的逐渐增强,BMP-7蛋白及mRNA水平(A％,30 d 95．87±1．19;180 d 26．43±1．26)逐渐降低,与对照组(A％,30 d 98．64±0．80;180 d 98．80±0．49)相比,差异有统计学意义(P<0．01或P<0．05);相反,肾组织中TGF-β1的mRNA (A％,30 d 40．26±0．98;180 d 102．12±6．45)及蛋白水平较对照组显著增加(P<0．01)。BMP-7与TGF-β1的蛋白及mRNA表达水平均呈显著负相关(P<0．01)。结论BMP-7可能是维持肾脏功能稳定的一个重要因子。BMP-7在糖尿病肾病中具有与TGF-β1相反的作用,其水平下降可能参与了糖尿病肾病早期小管间质的损伤。展开更多
基金This work was supported by the National Natural Science Foundation of China(No.30100220)
文摘Objective： Impaired signal transduction is associated with tumorigenesis and progression of various kinds of human cancers. Transforming growth factor （TGF）-beta/Smad and ras-mitogen activated protein kinase （MAPK） are two major signal transduction pathways for adjusting cell proliferation and differentiation. Little is known about TGF-beta/Smad4 in non-small cell lung cancer （NSCLC）. Hereby, we investigated the expression of Smad4 in NSCLC, its correlation with MAPK proteins （including p38, ERK1 and JNK1 proteins） and their clinical significance in NSCLC. Methods： The expressions of Smad4, p38, ERK1 and JNK1 were detected at protein level with Western blotting and immunohistochemistry, at transcription level with RT-PCR. Statistical analysis was performed for the comparisons of expressions of Smad4, p38, ERK1 and JNK1, and their correlation with various clinicopathological parameters and the prognosis of NSCLC. Results： The levels of protein and mRNA expression of Smad4 in lung cancer tissues were significantly lower than in normal tissues （P〈0.05）. All these four proteins were associated with TNM staging. There was a strongly negative correlation between p38 and Smad4. Expressions of Smad4, p38 and JNK1, as well as tumor differentiation and staging were significantly correlated with the prognosis of NSCLC by univariate analysis. By multivariate analysis, only Smad4, p38, tumor differentiation and staging were correlated with the prognosis. Taken together, the negative expression of p38 and positive expression of Smad4 were associated with a better prognosis of NSCLC. Conclusion： Smad4 could be of vital importance for the initiation and development of NSCLC. The expression of Smad4 might be inhibited by p38, supporting a cross-talk between main proteins of TGF-beta/Smad and ras-MAPK signal transduction pathways. Smad4 and p38 could be possible prognostic factors for NSCLC.
文摘目的观察糖尿病大鼠肾组织中骨形成蛋白7(BMP-7)的表达及探讨其在糖尿病肾病中的可能作用。方法将大鼠分为糖尿病组及正常对照组,分别在第30、60、90、120、150及180 d测定各组的血糖、Ser、24 h尿白蛋白、尿肌酐(Ucr)水平。以HE、PASM染色及ColⅣ蛋白表达衡量肾脏病理改变。用免疫组化及RT-PCR方法检测肾组织中BMP-7、TGF-β1的蛋白及mRNA表达水平。结果糖尿病组各时间点血糖、尿白蛋白量(24 h)均明显高于对照组(P<0．01)。糖尿病组伴随病理改变的加重和ColⅣ表达的逐渐增强,BMP-7蛋白及mRNA水平(A％,30 d 95．87±1．19;180 d 26．43±1．26)逐渐降低,与对照组(A％,30 d 98．64±0．80;180 d 98．80±0．49)相比,差异有统计学意义(P<0．01或P<0．05);相反,肾组织中TGF-β1的mRNA (A％,30 d 40．26±0．98;180 d 102．12±6．45)及蛋白水平较对照组显著增加(P<0．01)。BMP-7与TGF-β1的蛋白及mRNA表达水平均呈显著负相关(P<0．01)。结论BMP-7可能是维持肾脏功能稳定的一个重要因子。BMP-7在糖尿病肾病中具有与TGF-β1相反的作用,其水平下降可能参与了糖尿病肾病早期小管间质的损伤。
