去卵巢大鼠骨髓基质细胞beta-catenin蛋白表达变化观察

目的观察卵巢切除大鼠骨髓基质细胞(BMSC)beta-catenin蛋白表达的变化。方法将18只健康3月龄未经产雌性SD大鼠随机平分为去卵巢和假手术两个组。术后14周,取左侧股骨,新鲜分离骨髓细胞,静置贴壁法体外培养9d后,采用间接免疫荧光方法检测BMSC中beta-catenin蛋白表达和定位的变化。取右侧股骨,在双能直线χ-射线骨密度仪上检测骨密度的变化。结果大鼠去卵巢14周后,股骨近端和远端的骨密度显著下降(P<0.05),而股骨干的骨密度没有变化(P>0.05)。在体外培养的假手术组BMSC中,beta-catenin蛋白主要在胞核中表达。与假手术组相比,去卵巢组BMSC核中beta-catenin蛋白表达减少,而胞膜中表达增加。结论beta-catenin蛋白在卵巢切除大鼠BMSC核中表达的下降可能与绝经后骨质疏松症的发生有关。

UVB诱导人皮肤成纤维细胞中beta-catenin基因的变化研究

目的:观察中波紫外线(UVB)诱导人皮肤成纤维细胞中β-catenin及其下游基因c-myc的变化,探讨其在紫外线诱导光老化和肿瘤发生中的作用。方法:使用组织块法分离培养原代成纤维细胞,使用第2～8代人皮肤成纤维细胞进行紫外线处理,倒置荧光显微镜观察其形态学改变,β-gal半乳糖苷酶细胞衰老试剂盒染色衰老细胞、western blot检测衰老相关蛋白P16的表达,western blot检测紫外线处理人皮肤成纤维细胞各时相点β-catenin、c-myc蛋白表达水平,RT-PCR检测紫外线处理人皮肤成纤维细胞各时像点β-catenin、c-mycmRNA水平的表达变化。结果:40mJ/cm2UVB单次照射后可以诱导人皮肤成纤维细胞衰老,β-gal衰老染色阳性率达到约90%,衰老相关基因P16蛋白表达明显升高,β-catenin、c-myc蛋白表达水平和mRNA水平照射后较未照射组均明显降低。结论:紫外线UVB处理人皮肤成纤维细胞可以诱导其发生衰老改变,衰老细胞中β-catenin、c-myc表达水平明显降低,这些结果与皮肤黑色素细胞瘤相关基因改变的研究相近,为以后皮肤恶性肿瘤的研究提供了线索。

Wnt-1或Wnt/beta-catenin信号通路在恶性肿瘤中的研究进展

Wnt-1或Wnt/beta-catenin信号通路最初在鼠乳腺癌病毒诱导的乳腺癌发现的。大量研究发现,该通路异常导致人类各种肿瘤发生、发展,采用siRNA或Wnt-1抗体等手段调控该通路,显示出抗肿瘤效应。提示以Wnt-1或Wnt/beta-catenin为靶向的抗肿瘤治疗,值得进一步研究。

益气化瘀解毒法对慢性萎缩性胃炎伴异型增生大鼠APC、beta-catenin表达干预的实验研究

胃癌是一个逐步形成的过程，常由胃癌前病变（PLGC）进一步发展而来。胃癌前病变的早诊断和早干预可以阻断其向胃癌的发展。PLGC分为肠上皮化生（IM）和异型增生（Dys）两种，尤其是中重度异型增生。轻度Dys约15％～30％会进展为重度Dys和／或腺癌，而重度Dys的病人有60％～80％发展为胃癌。有效干预PLGC，阻断其向胃癌的发展，对防治胃癌有积极意义。

探讨HBV X、TGF-alpha,c-myc及beta-catenin基因与高发区肝癌的相关性

目的 研究HBVX基因、TGF alhpa、c myc、beta catenin等癌变相关基因及 2 49密码子突变的p5 3蛋白在高发区肝细胞癌癌变发生及其恶性表型维持所发挥的作用。方法 以肝癌高发区启东的肝癌细胞株 770 1和 770 3标本作为研究对象 ,以PCR及DNA测序分析方法确定HBVX基因在细胞DNA水平的整合。以RT PCR及Western blot检测HBVX基因的转录与表达。用PCR RFLP方法确定 p5 3基因 2 49密码子的错义突变。应用免疫组织化学法分析TGF alhpa ,c myc ,beta catenin的表达。结果 2株细胞在DNA水平都存在HBVX基因片断的整合 ,但未见完整的转录和蛋白水平表达。序列分析显示 2株细胞的HBVX基因的序列各有特异性 ,并存在 13 0、13 1密码子的热点突变。PCR RFLP分析说明 2个细胞株中p5 3基因 2 49密码子均属野生型。免疫组化显示 2株细胞中TGF alpha ,c myc和beta catenin蛋白均有显著的积累。 结论 本实验的结果显示HBVX基因对这 2株细胞恶性表型的维持并不存在必然的关联 ,而是 1种HBV感染的遗传标志。未见HBVX基因蛋白表达 ,可能由于X基因 3′端缺失变异所致。免疫组化的结果显示TGF alpha ,c myc和beta catenin蛋白的显著积累 ,说明多种癌基因的相互协同 ,可能与肝癌的发生。

Beta-catenin在颅内动脉瘤中的表达

目的通过观察Beta-连环蛋白(Beta-catenin)在颅内动脉瘤中的表达,探讨颅内动脉瘤发生、发展及破裂的相关因素。方法用免疫组织化学方法检测30例脑动脉瘤标本中Beta-catenin的表达,同时将5例正常脑动脉组织作为对照。结果Beta-catenin在正常脑动脉壁表达阳性,平均分值3.0±0.0;未破裂动脉瘤中表达稍弱,平均分值2.1±0.3;破裂动脉瘤壁表达最低,平均分值1.0±0.3,组间比较,差异有统计学意义(P<0.05)。结论Be-ta-catenin在颅内动脉瘤壁表达下降,在破裂动脉瘤壁仅有少量表达。Beta-catenin可能与颅内动脉瘤的形成和破裂密切相关。

Beta-Catenin,APC蛋白,C-myc及CyclinD_1在卵巢上皮肿瘤中的表达及意义

目的:探讨卵巢上皮性肿瘤的beta-catenin,APC蛋白及c-m yc,cyclin D1的表达及意义。方法:采用ABC免疫组织化学染色方法检测48例卵巢上皮性肿瘤(其中包括18例良性肿瘤,13例交界性肿瘤及17例恶性肿瘤)的beta-catenin,APC蛋白,c-myc及cyclinD1的表达。结果:beta-catenin在卵巢恶性上皮肿瘤及交界性上皮肿瘤中异常表达率均明显高于其在卵巢良性上皮性肿瘤中的表达(P<0.001)。抑癌基因APC蛋白在卵巢恶性上皮性肿瘤及交界性上皮肿瘤的表达明显低于卵巢良性上皮性肿瘤(P<0.05)。癌基因c-myc,cyclinD1在卵巢恶性上皮肿瘤及交界性上皮肿瘤中的表达均强于卵巢良性上皮肿瘤(P<0.05)。卵巢上皮性肿瘤中beta-catenin与APC蛋白呈负相关(P<0.05);beta-catenin与c-myc,cyclinD呈正相关(P<0.05)。结论:APC-beta-catenin-Tcf-4通路异常对卵巢上皮肿瘤的发生,发展起重要作用,beta-catenin异常表达可能激活原癌基因C-m yc,cyclin D1的表达。

TLR4信号缺失对MPTP帕金森小鼠模型黑质Beta-catenin信号的表达影响

目的观察帕金森小鼠模型中TLR4通路对Beta-catenin信号的表达影响。方法 C57BL小鼠和TLR4敲除(TLR4knock out,TLR4 KO)小鼠各36只,分别注射生理盐水和1-甲基-4-苯基-1,2,3,6-四氢吡啶(MPTP)。采用RT-PCR、Westernblot检测4组之间的Beta-catenin的m RNA和蛋白表达变化,进一步采用免疫荧光的方法检测黑质区星形胶质细胞中Beta-catenin的共表达变化。结果 RT-PCR及Western blot结果显示,与生理盐水注射组小鼠相比,C57BL、TLR4KO小鼠在MPTP注射后,mRNA和蛋白表达明显升高(P<0.01);并且,与C57BL小鼠MPTP注射组相比,TLR4KO小鼠MPTP注射组Beta-catenin的mRNA和蛋白表达明显升高(P<0.01)。进一步的免疫荧光结果显示,与C57BL小鼠MPTP注射组相比,TLR4KO小鼠MPTP注射组星形胶质细胞(GFAP)中表达的beta-catenin明显升高。结论 TLR4通路在亚急性帕金森MPTP模型中,对黑质beta-catenin蛋白的表达起重要调控作用,Toll样信号与Beta-catenin信号这种互动关系可能在帕金森发病机制中起着重要的作用。

Disordered beta-catenin expression and E-cadherin/CDH1 promoter methyiation in gastric carcinoma

瞄准：在胃的癌的原子核或膜 / 细胞质调查 beta-catenin 的分发房间，在 E-cadherin 基因甲基化之间的关系和它的表示，和象在预言肿瘤渗入的潜在的分子的标记的 beta-catenin 和 E-cadherin 的角色。方法：胃的癌的 29 个案例，分类同样弥漫、肠的变体，为学习被选择。原子、细胞质的蛋白质被净化， beta-catenin 内容被 ELISA 检测。E-cadherin/CDH1 基因倡导者的 DNA 甲基化被 methylation 特定的 PCR 和 compaired 学习， E-cadherin 表示由免疫组织化学检测了。结果：在胃的癌的 27 种情况中，在原子核和膜 / 细胞质之间的 beta-catenin 内容的比率与 T 分类被相关(r = 0.392， P = 0.043 ) 。意义在 T2 和 T3 组之间是在场的。没有关联以他们的 beta-catenin 分发在弥漫、肠的变体之间被检测。在胃的癌的弥漫的变体的 21 种情况中，在在 CDH1 基因甲醇化物组和甲醇化物得非的组之间的 E-cadherin 表示有差别(29 % 对 71 % ， P = 0.027 ) 。在 CDH1 基因甲基化和 T 分类之间的关联都没被发现，也不是在 E-cadherin 表示之间的意义，肿瘤渗入分级。结论：比较分析原子并且 membrane/cytoplasmic beta-catenin 能预言本地肿瘤渗入。E-cadherin/CDH1 基因甲基化是为它在弥漫的变体的基因沉默的一个重要原因胃的癌。当 E-cadherin 不在时的 CDH1 基因的甲基化是在胃的致癌作用的一个早事件。

Expression level of beta-catenin is associated with prognosis of esophageal carcinoma

AIM: To examine the association of beta-catenin with the clinicopathologic features and prognosis of esophageal squamous cell carcinoma (ESCC). METHODS: Beta-catenin mRNA expression level in 40 ESCC patients (28 males and 12 females, age range 38-82 years, median 60 years) was analyzed by real- time PCR. Beta-catenin mRNA expression levels in tumor cells were categorized as weaker (level 1) or equal to or stronger (level 2) than those in endothelial cells. We examined the correlation between the beta-catenin expression and the clinicopathological factors and prognosis of ESCC patients. RESULTS: Level 2 beta-catenin expression was found in 29 patients. ESCC with level 2 expression had a higher rate of lymphnode metastasis (0.0776 ± 0.0369 vs 0.3413 ± 0.1803, P < 0.001) and deeper tumor invasion (0.0751 ± 0.0356 vs 0.3667 ± 0.1928, P < 0.001), and a poorer survival rate (P = 0.0024) than ESCC with level 1 expression. CONCLUSION: Beta-catenin expression in ESCC is of great importance.

Overall expression of beta-catenin outperforms its nuclear accumulation in predicting outcomes of colorectal cancers

AIM: To examine the expression of beta-catenin in colorectal cancer and look for association with other clinico-pathological parameters. METHODS: Tumor samples from 163 cases of colorectal cancer (CRC) who had undergone primary colectomy between May,1998 and November,2002 with complete follow-up data for either 5 years or until death were recruited for a beta-catenin immunohistochemical study. The percentage of immunoreacted tumor cells was defined as overall staining density (OSD) and percentage of cells having nuclear localization was counted as nuclear staining density (NSD). Univariate exploration used log-rank test and multivariate survival analysis used Cox's hazard regression model. RESULTS: Beta-catenin immunoreactivity was detected in 161 samples (98.8%),of which 131 cases had nuclear staining. High OSD (≥ 75%),detected in 123 cases (75.5%),was significantly associated with earlier clinical staging (P < 0.01),lower nodal status (P = 0.02),non-metastatic status (P < 0.01) and better differentiation (P = 0.02). Multivariate analysis found that high OSD was independently associated with better survival [Cox's hazard ratio 0.51,95% confidence interval (CI) 0.31-0.83]. Although high NSD (≥ 75%) was correlated with high pre-operative serum CEA (P = 0.03),well differentiation (P < 0.01),and increased staining intensity (P < 0.01),the parameter was not significantly associated with survival. CONCLUSION: Unlike previous reports,the study did not find a predictive value of nuclear beta-catenin in CRC. Instead,the overall expression of beta-catenin in CRC showed an association with better differentiation and earlier staging. Moreover,the parameter also independently predicted superior survival.

E-cadherin and beta-catenin expression in Epstein-Barr virus-associated gastric carcinoma and their prognostic significance

AIM: To examine the role of E-cadherin and beta- catenin in carcinogenesis and to assess their prognostic implication in Epstein-Barr virus-associated gastric carcinomas (EBV-GCs). METHODS: We compared the frequency of E-cadherin and beta-catenin expression in 59 EBV-GCs and 120 non-EBV-GCs, and examined the association between patients' prognosis and the expressions of these proteins. RESULTS: Neither the cellular-membranous nor the cytoplasmic E-cadherin expression showed any difference between EBV-GCs and non-EBV-GCs. On the other hand, loss of membranous expression of beta- catenin occurred more frequently in non-EBV-GCs than EBV-GCs [odds ratio = 0.41; 95% confidence interval (CI), 0.19-0.90]. Furthermore, the nuclear and/or cytoplosmic expression of beta-catenin was seen more frequentlyin EBV-GCs than non-EBV-GCs (odds ratio = 2.23; 95% CI, 0.97-5.09), and was observed in a larger proportion of carcinoma cells of EBV-GCs than non-EBV-GCs (P = 0.024). Survival analysis for non-EBV-GC revealed that lymph node metastasis was significantly associated with poor prognosis (P < 0.001). Among EBV- GCs, the depth of invasion (P = 0.005), lymph node metastasis (P = 0.004) and an intestinal type by Lauren classification (hazard ratio = 9.47; 95% CI, 2.67-33.6) were significantly associated with poor prognosis. On the other hand, nuclear and/or cytoplasmic expression of beta-catenin was associated with a better prognosis in patients with EBV-GC (hazard ratio = 0.32; 95% CI, 0.11-0.93). CONCLUSION: We observed more frequent preservation of beta-catenin in cell membrane and accumulation in nuclei and/or cytoplasm in EBV-GCs than in non-EBV- GCs. Factors involved in the prognosis of EBV-GCs and non-EBV-GCs are different in the two conditions.

Expression of Wnt-1,beta-catenin and c-myc in Ovarian Epithelial Tumor and Its Implication

Objective:To investigate the expression of Wnt-1,beta-catenin and c-myc in normal ovarian epithelial cell and malignant ovarian epithelial tumor.Methods:Immunohistochemical staining with SP method was conducted to identify the expression of Wnt-1,beta-catenin and c-myc in 18 samples of normal epithelial tissue and 34 cases of malignant epithelial tumor of ovary.Results:The expression rate of Wnt-1 and c-myc in malignant epithelial tumors was higher than those in normal epithelial cell(P<0.05).The abnormal expression rate of beta-catenin in malignant ovarian epithelial tumors was higher than that in normal epithelial cell(P<0.05).A significant positive correlation was found between Wnt-1,beta-catenin and c-myc in malignant ovarian epithelial tumor(P<0.05).A significant difference of expressions of Beta-catenin and C-myc was found between serous and mucinous tumors (P<0.05).Conclusion:The abnormal expression of Wnt-1,beta-catenin and c-myc might indicate the malignant transformation in ovarian epithelial tumors.

Expressions of GSK-3beta,Beta-Catenin and PPAR-Gamma in Medulloblastoma

Objective:To investigate the expressions of GSK-3beta,Beta-catenin and PPAR-gamma,and their relationship in medulloblastoma,and to explore their value in clinic application. Methods:Immunohistochemical staining with SP method was conducted to determine the expressions of GSK-3beta,Beta-catenin and PPAR-gamma in 48 cases of medulloblastoma and 10 normal cerebellar tissues. Results:The rate of abnormal expressions of beta-catenin and PPAR-gamma in MB was higher than that in normal. Conversely,GSK-3beta in MB was lower than that in the normal (P<0.05). Furthermore,in medulloblastoma,beta-catenin and GSK-3beta showed a negative correlation,PPAR-gamma and beta-catenin had a positive correlation. Conclusion:Abnormal expression of beta-catenin plays a crucial role in the development of medulloblastoma. Meanwhile,PPAR-gamma and GSK-3beta which are tightly related with beta-catenin are both involved in the genesis and development of medulloblastoma.

Expressions of beta-catenin, APC Protein, C-myc and Cyclin D1 in Ovarian Epithelial Tumor and Their Implication

Objective: To investigate the expressions of beta-catenin, protein APC (adenomatous polyposis coli protein), c-myc and cyclin D1 and their implication in ovarian epithelial tumor. Methods: Immunohistochemical staining with SP method was conducted to identify the expressions of beta-catenin, APC protein, c-myc and cyclin D1 in ovarian epithelial tumor in 48 cases. Results: The abnormal expression rate of beta-catenin in malignant and borderline ovarian epithelial tumors was higher than that in benign epithelial tumors (P<0.01). The expression rates of c-myc and cyclin-D1 in ovarian malignant and borderline epithelial tumors were higher than those in benign epithelial tumors too(P<0.05). The prevalence of APC protein positive expression in benign epithelial tumors were significantly greater than that in malignant epithelial tumors (P<0.05). A significant negative correlation was found between beta-catenin and APC protein in ovarian epithelial tumors; while a significant positive correlation was found between beta-catenin, c-myc and cyclin-D1 in ovarian epithelial tumor (P<0.05). Conclusion: The abnormal expressions of Beta-catenin, APC protein, c-myc and cyclin-D1 might be used to indicate the malignance transform of ovarian epithelial tumors.

Expression of Beta-Catenin and APC Protein in Ovarian Epithelial Tumor and Its Implication

Objective: To investigate the expression of beta-catenin, APC protein and its implication in ovarian epithelial tumor. Methods: Immunohistochemical staining with SP method was conducted to determine the expression of beta-catenin and APC protein in 48 cases of ovarian epithelial tumor. Results: The abnormal expression rates of beta-catenin in ovarian malignant and borderline epithelial tumors were higher than that in benign epithelial tumors. The expression of APC protein in benign epithelial tumors was significantly greater than that in malignant epithelial tumors. A significant negative correlation was found between beta-catenin and APC protein in ovarian epithelial tumors. Conclusion: Beta-catenin and APC protein have important effect on pathogenesis and development of ovarian epithelial tumors.

Relationship between Expression of beta-catenin and VEGFs(VEGFA,VEGF-C),VEGF Receptors-2(VEGFR-2)in Medulloblastoma

Objective:To investigate the expression of beta-catenin and VEGFs(VEGF-A,VEGF-C)and VEGF receptor-2 (VEGFR-2)protein in medulloblastoma.Methods:Immunohistochemical staining with SP method was conducted to determine the expression of beta-catenin and VEGFs(VEGF-A,VEGF-C)and VEGFR-2 in 33 cases of medulloblastoma and 10 normal cerebellar tissues.Results:The expression rate of beta-catenin,and VEGFs (VEGF-A,VEGF-C)and VEGFR-2 in medulloblastoma were significantly higher than that in normal tissue.A significant positive correlation was found between beta-catenin and VEGFs(VEGF-A,VEGF-C)and VEGFR-2 protein in medulloblastoma.Conclusion:There was a correlation between beta-catenin and VEGFs(VEGF-A, VEGF-C)and VEGFR-2 in medulloblastoma,which may play a role in the pathogenesis and development of medulloblastoma.

Expressions of Beta-catenin,E-cadherin and MMP-7 in Ovarian Epithelial Tumors

目的将在卵巢的上皮细胞瘤调查 Beta-catenin， E-cadherin 和 MMP-7 和他们的含意的表情。与 SP 方法染色的方法 Immunohistochemical 被进行在 66 种情况中在卵巢的上皮细胞瘤识别 Beta-catenin， E-cadherin 和 MMP-7 的表情。结果在恶意的卵巢的上皮细胞瘤的 Beta-catenin 的反常表示率比在边线和良性的上皮细胞瘤(P【0.05 ) 的那些高。E-cadherin 在的积极的率良性并且边线卵巢的上皮细胞瘤在恶意的上皮细胞瘤比那显著地大。MMP-7 在的表示率恶意并且边线卵巢的上皮细胞瘤在良性的上皮细胞瘤(P【0.05 ) 比那高。Beta-catenin， E-cadherin 和 MMP-7 的反常表情可能被用来显示恶意的结论卵巢的上皮细胞瘤转变，但是他们没在卵巢的上皮细胞瘤与腹水侵略，胎膜侵略和附加侵略有重要关联。

Wnt-1、beta-catenin及C-myc在上皮性卵巢癌中的表达及意义

目的:探讨Wnt-1、beta-catenin及C-myc在正常卵巢及卵巢恶性上皮肿瘤中的表达。方法:运用免疫组织化学SP法检测18例正常卵巢组织及34例卵巢恶性上皮肿瘤中Wnt-1、beta-catenin及C-myc的蛋白表达。结果:18例正常卵巢中Wnt-1、C-myc阳性表达率为5.56%、16.67%,beta-catenin异常表达率为16.67%;34例卵巢恶性上皮肿瘤Wnt-1阳性表达率为94.11%,C-myc阳性表达率及beta-catenin异常表达率为100%。卵巢恶性上皮肿瘤Wnt-1、C-myc阳性率及beta-catenin异常表达率明显高于正常卵巢成熟细胞(P<0.05),且Wnt-1、beta-catenin及C-myc3者之间均存在显著正相关(P<0.05)。不同类型的恶性上皮肿瘤中,只有beta-catenin及C-myc在浆液性与黏液性肿瘤中的表达差异有统计学意义(P<0.05),Wnt-1、beta-catenin及C-myc与肿瘤有无浸润无关(P>0.05)。结论:Wnt信号传导通路中Wnt-1、beta-catenin及C-myc的改变与卵巢上皮肿瘤的恶化有关,而与肿瘤的浸润无明显相关。