Expression of FRAT1 and β-catenin in human brain glioma and their significances

Objective: To investigate the expression of FRAT1 and β-catenin in human brain glioma, analyze the correlation between the expression and clinical pathological grades and the correlation of the two genes. Methods: FRAT1 and β-catenin were detected by immunohistochemistry in 84 human brain glioma tissues and 6 human normal brain tissues. Results: 66.7% (56/84) and 77.4% (65/84) of human brain glioma tissues expressed FRAT1 and β-catenin protein, whereas no FRAT1 and β-catenin protein expression was detected in human normal brain tissues. The expression levels of FRAT1 and β-catenin increased markedly with the ascending of pathologic grade of tumor specimens (r = 0.55, P < 0.01, r = 0.70, P < 0.01), there was a positive correlation between FRAT1 and β-catenin (r = 0.77, P < 0.01). Conclusion: FRAT1 and β-catenin over-expression maybe closely related with occurrence and development of human brain gliomas. The results provide important supplements for the research of Wnt/β-catenin pathway. Meanwhile, FRAT1 may act as a valuable biomarker for molecular diagnosis of glioma and a potential target for gene therapy of glioma.     

Caveolin-1, E-cadherin and β-catenin in gastric carcinoma, precancerous tissues and chronic non-atrophic gastritis

Objective:To investigate the expressions of caveolin-1,E-cadherin and β-catenin in gastric carcinoma,precancerous gastric and chronic non-atrophic gastritis tissues,and evaluate the correlation of these expressions with the development of gastric cancer.Methods:The expressions of caveolin-1,E-cadherin and β-catenin were detected by biotin-streptavidin-peroxidase(SP) immunohistochemistry on 58 gastric cancer tissues,40 precancerous gastric tissues and 42 chronic non-atrophic gastritis tissues.The correlation between the expressions of caveolin-1,E-cadherin and β-catenin,and the clinicopathologic parameters of gastric cancer was analyzed retrospectively.Results:The positive rates of caveolin-1 and E-cadherin expressions in gastric carcinoma were significantly lower than precancerous gastric and chronic non-atrophic gastritis tissues(P<0.01).An abnormal rate of β-catenin expression in gastric carcinoma was higher than precancerous gastric and chronic non-atrophic gastritis tissues(P<0.01).Moreover,low expressions of caveolin-1,E-cadherin and β-catenin correlated with tumor size,depth of invasion,lymph node metastasis and TNM stage(P<0.05).The positive rates of caveolin-1 and E-cadherin expressions decreased(P<0.01),while an abnormal rate of β-catenin expression increased inversely,with the degree of atypical hyperplasia(P<0.01).Caveolin-1 expression correlated positively with E-cadherin(r=0.41,P<0.05).Caveolin-1(r= 0.36,P<0.05) and E-cadherin(r= 0.45,P<0.05) expressions negatively correlated with abnormal β-catenin expression.Conclusion: These results suggested that dysregulated expressions of caveolin‐1, E‐cadherin and β‐catenin correlated with the development of gastric cancer and its biological behavior.     

RELATIONSHIP BETWEEN THE EXPRESSIONS OF LMP1 AND ECADHERIN/β-CATENIN IN NASOPHARYNGEAL CARCINOMA

The Epstein-Barr virus (EBV) encoded latent membrane protein 1 (LMP1) is able to immortalize B-lymphocytes and malignantly transform rodent fibroblasts as well as human epithelial cells[1], thus confirmed as a carcinogenic protein nowadays. The LMP1 protein could activate NF-kB, AP1-1 and JNK[2] via its C terminal domain to take part in various signal-transduction pathways[3]. LMP1 could inhibit the differentiation of human epithelial cells[4, 5] and affect the proliferation and apopt…     

p120 Catenin Translocation is Involved in Enhancement of Hepatoma Cellular Malignant Features

OBJECTIVE To investigate the relationship between p 120^ctn translocation and hepatocellular carcinoma cell malignant features and the relationship between p 120^ctn and β-catenin translocation in cell signaling. METHODS Human hepatocellular carcinoma cells were over expressed with p120^ctn isoform 3A using a DNA transfection method. The effects of transfection and expression of p120^ctn and its binding capacity to E-cadherin were examined using immunoprecipitation and immunoblotting methods. p120^ctn subcellular localization and its relation with β-catenin were detected using immunofluorescent microscopy, p120^ctn phosphorylation was produced by EGF treatment. Cell adhesion, cell migration and cell proliferation were also examined in this study. RESULTS We found that p 120^ctn expression was increased after transfection and the binding capacity of p120^ctn to E-cadherin was enhanced. Tyrosine phosphorylation of p120^ctn increased after transfection and EGF treatment. p120^ctn and β-catenin cellular localization displayd a membrane and cytoplasmic expression pattern, but they translocated into the nucleus for relocalization after p120^ctn overexpression plus EGF stimulation. Cell adhesion ability was increased and migration ability reduced after transfection without EGF. Following transfection without EGF cellular proliferation was reduced, but increased after EGF treatment. CONCLUSION Our results suggest that p120^ctn plays an important role in hepatocellular carcinoma cell adhesion, migration and proliferation. In addition there is a relationship between p120^ctn and β-catenin subcellular localization and signaling.     

人胰腺癌组织中Tbx2蛋白的表达及Wnt/β-catenin信号通路对TBX2基因的调节

Objective:To investigate the expression of Tbx2 protein in pancreatic cancer tissues and its molecular regulation mechanism by Wnt/β-catenin signaling.Methods:49 pancreatic cancer and 13 non-cancer tissue specimens were obtained and examined the expression of Tbx2,and the correlation between the expression of Tbx2 and clinicopathological parameters was analyzed.The immunohistochemistry,immunocytochemistry,RT-PCR and Western blot assay methods were used to detect the changes of expression levels of β-catenin and Tbx2.Results:Tbx2 was amplified in 34 of 49 pancreatic cancers,and in 13 non-cancer tissues,only one sample amplified.The further study demonstrated that Tbx2 had a significant positive correlation with tumor differentiation degree and clinical stage,but it did not relate to the sex,age and the disease region.Inhibition of β-catenin degradation through the treatment of pancreatic cancer cells SW1990 with different concentrations of lithium chloride indicated that accumulation of β-catenin was sufficient to induce TBX2 expression.Conclusion:TBX2 gene plays an important role in the occurrence and development of pancreatic cancer and the accumulation of β-catenin contributes to the expression of TBX2.The Wnt/β-catenin signaling pathway participates the regulation of TBX2 in pancreatic cancer cells.     

Pin1、β-连接素和细胞周期素D1在老年肺癌组织中的表达及临床意义

Objective:To investigate the expressions and correlations of Pin1,β-catenin and cyclin D1 in elderly lung carcinomas.Methods:The expressions of Pin1,β-catenin and cyclin D1 were examined in the specimens of 92 elderly lung carcinomas and 10 normal lung tissues by immunohistochemistry and explored the relationship between the expression levels and clinicopathological factors.Results:(1) The overexpression of Pin1 and cyclin D1 in lung carcinomas was 46 (50%)cases and 60 (65.22%) cases respectively and 56 (60.82%) cases showed positive immunoreactivity for β-catenin in the nuclear and (or) cytoplasmic fraction in tumor tissues,In normal tissue,the expressions of Pin1 and cyclin D1 were negative,the expression of β-catenin was lied in cell membrane.(2) In lung carcinomas the expressions of Pin1,β-catenin and cyclin D1 correlated with tumor differentiation (P＜0.05).The pesitive expression rate and intensity of Pin1 correlated with tumor stage (P=0.032) and lymph node positive disease (P=0.041).The expression of β-catenin correlated with lymph node positive disease (P=0.012).(3) High expression levels of Pin1 correlated with aberrant β-catenin expression (P=0.000) but did not show a correlation with cyclin D1 (P=0.157).Conclusion:In elderly lung carcinomas,the positive expression of Pin1 causes abnormal accumulation of β-catenin and actives its target gene,however,this target gene was not cyclin DI.The detection of Pin1 expression had some clinical significance in estimating prognosis of elderly patient with lung carcinomas.     

E钙粘蛋白、α-catenin、β-catenin在人肺腺癌组织中的表达

目的　探讨E钙粘蛋白 (ECD)、α catenin(α cat)及 β catenin( β cat)在人肺腺癌组织中的表达与肺腺癌分化、转移的关系。方法　采用免疫组化的方法 ,对 5 7例肺原发腺癌和 2 7例淋巴结转移癌的ECD、α cat、β cat进行了半定量分析。结果　ECD在低分化组中表达明显低于高分化组 ,在淋巴结转移癌中同样与分化相关 ,但原发癌ECD的表达与淋巴结转移的发生无关。α cat和 β cat在低分化组中的表达也明显低于高分化组 (P <0 .0 5 ) ,且两者在原发癌中表达的下调与淋巴结转移癌的发生有着明显的相关性 (P <0 .0 5 )。结论　ECD、α cat、β cat表达的减少伴随着肺腺癌的去分化 ,并且α cat、β cat表达异常和淋巴结转移癌有极幂切的相关性。     

siRNA抑制β-catenin表达在骨肉瘤MG63细胞系中的作用

背景与目的:β-catenin蛋白是WNT信号通路的核心蛋白,与多种肿瘤的发生相关,然而在骨肉瘤中所扮演的角色却仍未阐明.本研究通过抑制β-catenin基因在骨肉瘤细胞系MG63中的表达,探讨β-catenin对细胞的生长、凋亡及肿瘤侵袭等方面的作用.方法:设计合成β-catenin的siRNA序列,LipofectamineTM2000转染入MG63细胞.采用RT-PCR和Western blot检测β-catenin在干扰后的mRNA和蛋白表达情况,利用流式细胞仪检测细胞周期及凋亡,CCK-8检测细胞增殖,transwe11法检测细胞侵袭能力.结果:RT-PCR和Western blot检测β-catenin mRNA和蛋白表达,实验组较对照组显著降低.细胞周期检测,实验组较对照组无明显差异(P＞0.05).但凋亡检测,实验组较对照组显著增加(P＜0.05).CCK-8法检测实验组较对照组略有降低,但差异无统计学意义(P＞0.05).Transwell法结果显示,实验组侵袭能力显著下降,差异有统计学意义(P＜0.05).结论:特异性干扰β-eatenin基因表达可抑制骨肉瘤侵袭能力,并促进肿瘤细胞凋亡.     

p120-catenin通过Kaiso在转录水平上调控肺癌细胞系LTEP-a-2中β-catenin的表达

目的:探讨肺癌细胞系中p120-catenin（p120ctn）调节β-catenin转录的分子机制。推测p120ctn可能通过其分子伴侣Kaiso进而发挥调节β-catenin转录的重要功能。方法:转染、Real-Time PCR、BSP测序、染色质免疫共沉淀及蛋白质免疫共沉淀等多种研究方法验证我们的推测。结果:对肺癌细胞系中β-catenin启动子区域的测序结果发现,LTEP-a-2中存在着可能与Kaiso结合的甲基化的CpG双核苷酸序列和KBS序列。去甲基化试剂5-Aza-CdR能使肺癌细胞系中β-catenin的mRNA表达明显上调。转染Kaiso后,肺癌细胞系中Kaiso的高表达可明显下调β-catenin的mRNA表达。用5-Aza-CdR处理肺癌细胞系后再转染Kaiso,细胞系中β-catenin的mRNA表达上调。染色质免疫共沉淀结果显示LTEP-a-2中Kaiso只能够与甲基化的CpG双核苷酸序列结合而不与KBS序列结合;蛋白质免疫共沉淀显示Kaiso能够与p120ctn结合。结论:肺癌细胞系LTEP-a-2中p120ctn调节β-catenin的转录是通过转录抑制因子Kaiso与β-catenin启动子区域甲基化的CpG双核苷酸序列而实现的。     

β-catenin与恶性肿瘤关系的研究进展

β-连环素（β—catenin，β—cat）作为胞浆内的一种重要多功能蛋白，具有介导细胞粘附和在Wnt信号传导途径中起重要作用的双重功能。目前对恶性肿瘤的研究表明，β—catenin基因突变及蛋白的过表达与肿瘤的发生、发展和预后密切相关，阻断β—catenin信号通路的异常激活有望成为治疗恶性肿瘤的新手断。     

DNMT1高表达与beta-catenin蓄积及肺鳞癌、腺癌的恶性表型相关

背景与目的 DNA甲基转移酶1(DNA methyltransferase 1,DNMT1)是调控DNA甲基化的重要分子之一,DNMT1的异常表达与抑癌基因的甲基化、失活和多种肿瘤的发生发展有关.本研究旨在分析阐明DNMT1在正常肺组织和肺癌组织中表达的差异及其与肺鳞癌和腺癌临床病理因素的关系,并探讨DNMT1与β-catenin在肺癌中表达的相关性.方法采用组织芯片和免疫组化方法检测DNMT1和β-catenin在84例肺鳞癌、腺癌和相应癌旁正常肺组织中的表达情况.结果 DNMT1在84例肺癌组织中的平均阳性率为(58.04±35.07)%,显著高于癌旁正常肺组织[(6.88±10.26)%](t=12.835,P<0.001).DNMT1的高表达与肺癌组织的腺癌组织学分型(r=0.365,P=0.001)、低 分化程度(r=0.253,P=0.021)和淋巴结转移(r=0.246,P=0.024)正相关.DNMT1 与β-catenin的细胞浆表达显著正相关(r=0.571,P<0.001).结论 DNMT1的高表达是肺鳞癌和腺癌的普遍现象,DNMT1的高表达与肺癌的腺癌组织学类型和恶性表型有关;DNMT1在肺癌中可能与β-catenin协同表达.     

桑根皮素调控Wnt/β-catenin信号通路影响胶质瘤U251细胞增殖的实验研究

目的 探讨桑根皮素调控Wnt/β-catenin信号通路对脑胶质瘤U251细胞增殖的影响.方法 体外培养人脑胶质瘤细胞U87,采用不同浓度桑根皮素(1、5、25、50、100μmol/L)作用于U87细胞,分别采用MTT法、细胞集落形成法、流式细胞术检测细胞增殖和凋亡活性.采用Western blotting法和细胞免...     

p120ctn家族成员δ－catenin与常见恶性肿瘤关系的研究进展

细胞黏附分子Catenin家族成员之一δ－catenin（也被称为NPRAP,neural plakophilin－related armadillo protein）最初被发现主要表达于神经元突触,它对突触的形态结构和功能维持起重要作用。随着研究的不断深入,δ－catenin与恶性肿瘤之间的关系逐渐受到研究者的关注,且现有的研究结果揭示δ－catenin在肿瘤组织中表达增高并与肿瘤患者的不良预后密切相关。本文主要综述了δ－catenin在肺癌、前列腺癌、乳腺癌、食道癌、结直肠癌等几个常见恶性肿瘤中的表达情况及其临床意义,为下一步深入研究δ－catenin促进肿瘤侵袭转移的机制奠定了基础。     

Wnt通路成员APC、β-catenin、c-myc及黏附分子E-cadherin与大肠癌的关系

大肠癌是我国十分常见的恶性肿瘤,其发病率占全部胃肠肿瘤的第一至第二位。随着我国人民生活水平的提高及生活方式、饮食、环境因素的变化,我国大肠癌的发病率已呈明显上升的趋势。大肠癌的发生、发展机理至今尚未十分清楚,“正常结直肠上皮—畸变性腺窝灶—腺瘤性息肉—腺瘤恶变—侵袭性癌”病理转变是一个多阶段、多基因参与的过程,涉及到癌基因的激活和抑癌基因的失活。近年来,分子生物学研究发现,Wnt通路中各癌基因、抑癌基因及细胞黏附分子异常与大肠癌的发生、发展密切相关。一、Wnt通路、黏附分子的组成及与肿瘤的关系Wnt基因编码…     

Frat与β-连环素在肺癌中的表达及与临床病理因素的关系

背景与目的Frat(frequently rearranged in advanced T-cell lymphomas)是Wnt(wingless/int)信号传导途径的正向调节因子,通过结合糖原合成酶激酶3(glycogen synthase kinase,GSK3),抑制GSK3依赖的磷酸化作用,从而阻止β-连环素(β-catenin)的降解,β-catenin通过与TCFs(T cell factors)结合而激活靶基因。本研究的目的是探讨Frat和β-catenin在肺癌中的表达及其与各临床病理因素的关系。方法采用组织芯片和免疫组织化学法检测52例肺癌标本中Frat和β-catenin的表达。结果Frat的阳性表达率为75.00%,其中高分化,中分化和低分化非小细胞肺癌(non-small cell lung cancer,NSCLC)中Frat的阳性率分别为41.67%(5/ 12),83.33%(15/18)和88.24%(15/17),差异有统计学意义(x~2=9.229,P=0.01)。β-catenin的细胞表达异常率为71.15%,高分化,中分化和低分化NSCLC中β-catenin的表达异常率分别为41.67%(5/12),61.11%(11/18)和100%(17/17),差异有统计学意义(x~2=12.601,P=0.002)。结论β-catenin的细胞表达异常与NSCLC的低分化正相关,Frat的表达与NSCLC的低分化和β-catenin的表达异常正相关。     

广西人肝细胞癌β—catenin基因突变及蛋白表达

目的研究广西地区人肝细胞癌发生、发展过程中β-catenin基因突变和蛋白表达状况。方法采用PCR联合基因直接测序法,检测108例肝细胞癌癌组织中β-catenin基因的突变;同时采用免疫组化方法检测β—catenin蛋白的表达状况。结果108例HCC癌组织中仅有12例发生β-catenin基因突变,突变率为11．1％。108例HCC癌组织中β—catenin蛋白阳性表达率为70．0％（75／108）,其中14．6％（11／75）为细胞核阳性;57．3％（43／75）为细胞质阳性;28．0％（21／75）为细胞膜阳性。β—catenin蛋白在12例有突变的样本中表达阳性率为100％。结论广西地区肝癌中β—catenin基因突变率比较低;β—catenin基因突变可能为导致β—catenin蛋白过表达的因素之一,并参与了肝癌癌变过程。     

广西人肝细胞癌β-catenin基因突变及蛋白表达

目的研究广西地区人肝细胞癌发生、发展过程中β-catenin基因突变和蛋白表达状况。方法采用PCR联合基因直接测序法,检测108例肝细胞癌癌组织中β-catenin基因的突变;同时采用免疫组化方法检测β-catenin蛋白的表达状况。结果 108例HCC癌组织中仅有12例发生β-catenin基因突变,突变率为11.1%。108例HCC癌组织中β-catenin蛋白阳性表达率为70.0%(75/108),其中14.6%(11/75)为细胞核阳性;57.3%(43/75)为细胞质阳性;28.0%(21/75)为细胞膜阳性。β-catenin蛋白在12例有突变的样本中表达阳性率为100%。结论广西地区肝癌中β-catenin基因突变率比较低;β-catenin基因突变可能为导致β-catenin蛋白过表达的因素之一,并参与了肝癌癌变过程。