To examine phosphatase and tensin homology deleted in chromosome 10 (PTEN),hypoxia-inducible factor-1 alpha (HIF-1 alpha) gene expressions and their relation to vascular endothelial growth factor(VEGF) protein express...To examine phosphatase and tensin homology deleted in chromosome 10 (PTEN),hypoxia-inducible factor-1 alpha (HIF-1 alpha) gene expressions and their relation to vascular endothelial growth factor(VEGF) protein expression in the patients with human colorectal adenomas and adenocarcinomas.Methods The expression of PTEN,HIF-1 alpha gene was detected by using in situ hybridization,and the VEGF expression levels by immunohistochemistry in colorectal adenomas and primary colorectal adenocarcinoma.Results Strong expression of HIF-1 alpha was detectable in the majority of colorectal dadenocarcinoma,particularly surrounding areas of necrosis in adenocarcinoma.PTEN,HIF-1 alpha mRNA and VEGF protein were positive in 51.6%,67.7% and 59.7% respectively in 62 cases of adenocarcinomas,and 77.8%,44.4% and 33.3% respectively in 18 cases of adenomas.The positive rate of VEGF was higher in the patients with colorectal adenocarcinomas than that in those with adenomas,whereas that of PTEN mRNA was contrary.HIF-1 mRNA expression was correlated significantly with lymph node metastasis,liver metastasis,Duke’s stage and recurrence.During colorectal tumor progression,the expression of HIF-1 alpha mRNA was positively correlated with the VEGF protein expression (χ2= 4.751 ,P<0.05),but negatively with the PTEN mRNA expression(χ2=21.84,P<0.01).Conclusion The absence or low expression of PTEN and the increased levels of HIF-1α and VEGF may paly an important role in carcinogenesis and progression of colorectal carcinoma.These results suggest that VEGF upregulated by HIF-1 alpha gene may be involved in angiogenesis of colorectal adenocarcinoma.4 refs,1 tab.展开更多
AIM To evaluate the effects of phosphatase and tension homologue deleted on chromosome ten(PTEN) gene on collagen metabolism in hepatic fibrosis and the underlying mechanisms.METHODS rat primary hepatic stellate cells...AIM To evaluate the effects of phosphatase and tension homologue deleted on chromosome ten(PTEN) gene on collagen metabolism in hepatic fibrosis and the underlying mechanisms.METHODS rat primary hepatic stellate cells(HSCs) and human LX-2 cells were transfected with adenovirus containing c DNA constructs encoding wild-type PTEN(Ad-PTEN), PTEN mutant G129 E gene(Ad-G129E), and r NA interference constructs targeting the PTEN sequence PTEN short hairpin r NA to up-regulate and downregulate the expression of PTEN. HSCs were assayed using fluorescent microscopy, real-time polymerase chain reaction, and western blotting. Moreover, a CCl_4-induced rat hepatic fibrosis model was established to investigate the in vivo effects. Hematoxylin and eosin, and Masson's trichrome were used to assess the histological changes. The expression of collagen Ⅰ and Ⅲ was assessed using immunohistochemistry and western blot analysis.RESULTS Elevated expression of PTEN gene reduced serum levels of alanine transaminase and aspartate transaminase, decreased collagen deposition in the liver, and reduced hepatocyte necrosis. In contrast, knockdown of PTEN expression had an opposite effect, such as increased collagen deposition in the liver, and was molecularly characterized by the increased expression of matrix metalloproteinase(MMP)-13(P < 0.01) and MMP-2(P < 0.01), as well as decreased expression of the tissue inhibitor of metalloproteinase(TIMP)-1(P < 0.01) and TIMP-2(P < 0.01).CONCLUSION These data indicated that gene therapy using recombinant adenovirus encoding PTEN might be a novel way of treating hepatic fibrosis.展开更多
目的:探讨抑癌基因纤黏连蛋白(fibronectin,FN)、张力蛋白同源基因蛋白(phosphatase and tensin homology deleted on chromosome ten,PTEN)在肝细胞性肝癌(hepatocellular carcinoma,HCC)组织中的表达及其临床意义。方法:收集215例HCC...目的:探讨抑癌基因纤黏连蛋白(fibronectin,FN)、张力蛋白同源基因蛋白(phosphatase and tensin homology deleted on chromosome ten,PTEN)在肝细胞性肝癌(hepatocellular carcinoma,HCC)组织中的表达及其临床意义。方法:收集215例HCC、癌旁组织和19例正常肝组织,用RT-PCR、Western blot、免疫组化SP法检测FN、PTEN m RNA和蛋白表达,分析FN和PTEN表达与HCC临床病理特征的关系。结果:肝癌组织中FN m RNA和蛋白表达均明显高于癌旁组织及正常肝组织(F=142.334,P=0.000);而PTEN低于癌旁组织及正常肝组织,且在癌旁组织中的表达亦明显低于正常肝组织(F=80.861,P=0.000)。FN表达阳性患者组较阴性患者组生存时间短;而PTEN表达阳性患者较阴性患者生存时间长,且在1年以后两者生存期有统计学意义(P<0.05)。结论:HCC癌组织中FN、PTEN在肝癌组织中存在异常表达,两者异常表达可能在肝癌的发生发展、侵袭转移中起一定的促进或抑制作用。展开更多
10号染色体同源丢失性磷酸酶与张力蛋白(phosphatase and tensin homology deleted on chromosome ten,PTEN)基因在子宫内膜癌中的严重丢失,是探讨子宫内膜癌发病机制的研究热点。PTEN基因通过影响下游磷脂酰肌醇3激酶/蛋白激酶B(phosph...10号染色体同源丢失性磷酸酶与张力蛋白(phosphatase and tensin homology deleted on chromosome ten,PTEN)基因在子宫内膜癌中的严重丢失,是探讨子宫内膜癌发病机制的研究热点。PTEN基因通过影响下游磷脂酰肌醇3激酶/蛋白激酶B(phosphatidylinositol 3-kinase/protein kinase B,PI3K/Akt)/哺乳动物雷帕霉素靶向(mammalian target of rapamycin,mTOR)、黏着斑激酶(focal adhesion kinase,FAK)和丝裂原激活蛋白激酶(mitogen-activated protein kinase,MAPK)这3条信号途径来调节细胞的生长、增殖、凋亡以及血管生长等,该基因发生丢失或突变均可导致肿瘤的发生。本文就PTEN基因和表皮生长因子受体(epidermal growth factor receptor,EGFR)信号通路及其下游信号通路的联系与子宫内膜癌发生发展研究的最新进展进行综述,为子宫内膜癌的基因诊断和治疗提供理论参考。展开更多
文摘To examine phosphatase and tensin homology deleted in chromosome 10 (PTEN),hypoxia-inducible factor-1 alpha (HIF-1 alpha) gene expressions and their relation to vascular endothelial growth factor(VEGF) protein expression in the patients with human colorectal adenomas and adenocarcinomas.Methods The expression of PTEN,HIF-1 alpha gene was detected by using in situ hybridization,and the VEGF expression levels by immunohistochemistry in colorectal adenomas and primary colorectal adenocarcinoma.Results Strong expression of HIF-1 alpha was detectable in the majority of colorectal dadenocarcinoma,particularly surrounding areas of necrosis in adenocarcinoma.PTEN,HIF-1 alpha mRNA and VEGF protein were positive in 51.6%,67.7% and 59.7% respectively in 62 cases of adenocarcinomas,and 77.8%,44.4% and 33.3% respectively in 18 cases of adenomas.The positive rate of VEGF was higher in the patients with colorectal adenocarcinomas than that in those with adenomas,whereas that of PTEN mRNA was contrary.HIF-1 mRNA expression was correlated significantly with lymph node metastasis,liver metastasis,Duke’s stage and recurrence.During colorectal tumor progression,the expression of HIF-1 alpha mRNA was positively correlated with the VEGF protein expression (χ2= 4.751 ,P<0.05),but negatively with the PTEN mRNA expression(χ2=21.84,P<0.01).Conclusion The absence or low expression of PTEN and the increased levels of HIF-1α and VEGF may paly an important role in carcinogenesis and progression of colorectal carcinoma.These results suggest that VEGF upregulated by HIF-1 alpha gene may be involved in angiogenesis of colorectal adenocarcinoma.4 refs,1 tab.
基金Supported by the National Natural Science Foundation of China,No.30872513
文摘AIM To evaluate the effects of phosphatase and tension homologue deleted on chromosome ten(PTEN) gene on collagen metabolism in hepatic fibrosis and the underlying mechanisms.METHODS rat primary hepatic stellate cells(HSCs) and human LX-2 cells were transfected with adenovirus containing c DNA constructs encoding wild-type PTEN(Ad-PTEN), PTEN mutant G129 E gene(Ad-G129E), and r NA interference constructs targeting the PTEN sequence PTEN short hairpin r NA to up-regulate and downregulate the expression of PTEN. HSCs were assayed using fluorescent microscopy, real-time polymerase chain reaction, and western blotting. Moreover, a CCl_4-induced rat hepatic fibrosis model was established to investigate the in vivo effects. Hematoxylin and eosin, and Masson's trichrome were used to assess the histological changes. The expression of collagen Ⅰ and Ⅲ was assessed using immunohistochemistry and western blot analysis.RESULTS Elevated expression of PTEN gene reduced serum levels of alanine transaminase and aspartate transaminase, decreased collagen deposition in the liver, and reduced hepatocyte necrosis. In contrast, knockdown of PTEN expression had an opposite effect, such as increased collagen deposition in the liver, and was molecularly characterized by the increased expression of matrix metalloproteinase(MMP)-13(P < 0.01) and MMP-2(P < 0.01), as well as decreased expression of the tissue inhibitor of metalloproteinase(TIMP)-1(P < 0.01) and TIMP-2(P < 0.01).CONCLUSION These data indicated that gene therapy using recombinant adenovirus encoding PTEN might be a novel way of treating hepatic fibrosis.
文摘目的:探讨抑癌基因纤黏连蛋白(fibronectin,FN)、张力蛋白同源基因蛋白(phosphatase and tensin homology deleted on chromosome ten,PTEN)在肝细胞性肝癌(hepatocellular carcinoma,HCC)组织中的表达及其临床意义。方法:收集215例HCC、癌旁组织和19例正常肝组织,用RT-PCR、Western blot、免疫组化SP法检测FN、PTEN m RNA和蛋白表达,分析FN和PTEN表达与HCC临床病理特征的关系。结果:肝癌组织中FN m RNA和蛋白表达均明显高于癌旁组织及正常肝组织(F=142.334,P=0.000);而PTEN低于癌旁组织及正常肝组织,且在癌旁组织中的表达亦明显低于正常肝组织(F=80.861,P=0.000)。FN表达阳性患者组较阴性患者组生存时间短;而PTEN表达阳性患者较阴性患者生存时间长,且在1年以后两者生存期有统计学意义(P<0.05)。结论:HCC癌组织中FN、PTEN在肝癌组织中存在异常表达,两者异常表达可能在肝癌的发生发展、侵袭转移中起一定的促进或抑制作用。
