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Reduced expression ofβ-catenin inhibitor Chibby in colon carcinoma cell lines

World Journal of Gastroenterology 2006年第10期12卷 1529-1535页

作者： Marion M Schuierer Elisabeth Graf Ken-Ichi Takemaru Wolfgang Dietmaier Anja-Katrin Bosserhoff Institute of Pathology University of Regensburg Franz-Josef-Strauss-Alice 1193053 RegensburgGermany Department of Pharmacology BST 7-168 Stony BrookNY 11794-8651United States Institute of Pathology University of Regensburg Franz-Josef-Strauss-Allee 1193053 RegensburgGermany

AIM： To analyse the Chibby expression and its function in colon carcinoma cell lines and colorectal carcinoma （CRC）. METHODS： Chibby expression levels were investigated by quantitative RT-PCR in a panel of seven different colon carcinoma cell lines. By sequencing, we analysed mutational status of Chibby. To test whether Chibby exhibited effects on β-catenin signalling in colon carcinoma cells, we transfected SW480 cells with Chibby expression plasmid and, subsequently, analysed activity of β-catenin and tested for alterations in cellular phenotype. In addition, we examined Chibby mRNA levels in samples of colorectal carcinomas and adjacent normal tissues by using quantitative RT-PCR and hybridised gene chips with samples from CRC and normal tissues. RESULTS： Chibby mRNA expression was strongly downregulated in colon carcinoma cell lines in comparison to normal colon epithelial cells and no mutation in any of the examined colon carcinoma cell lines was found. Further, we could show that Chibby inhibited β-catenin activity in TOPflash assays when over-expressed in SW480 cells. Proliferation and invasion assays with Chibby transfected SW480 cells did not reveal profound differences compared to control cells. In contrast to these in vitro data, quantitative RT-PCR analyses of Chibby mRNA levels in CRC tumor samples did not show significant differences to specimens in adjacent non-cancerous tissue. Consistent with these findings, gene chips analysing tissue samples of tumors and corresponding normal tissue did not show altered Chibby expressionCONCLUSION： Altered Chibby expression might be observed in vitro in different colon carcinoma cell lines. However, this finding could not be confirmed in vitro in CRC tumors, indicating that Chibby is not likely to promote CRC tumor development or progression. As Chibby is an important inhibitor of β-catenin signalling, our data implicate that the usability of colon carcinoma cell lines for in vitro studies analysing the Wnt/β-ca

关键词： Chibby Wnt β-catenin Colorectal carcinoma Colon carcinoma cell lines

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P120ctn overexpression enhances β-catenin-E-cadherin binding and down regulates expression of survivin and cyclin D1 in BEL-7404 hepatoma cells

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World Journal of Gastroenterology 2006年第8期12卷 1187-1191页

作者： Chao-Zan Nong Li-Li Pan Wei-Sheng He Xi-Liang Zha Hai-HongYe Hua-Yi Huang Department of Experimental Center Guangxi Hospital tor Nationalities Nanning 530001 Guangxi ZhuangAutonomous Region China Department of Biochemistry and Molecular Biology Fudan University Shanghai Medical College Shanghai200032 China

AIM:To understand the role of P120ctn in E-cadherin-mediated cell-cell adhesion and signaling as well as inhepatoma cell biological ***:We stably overexpressed p120ctn isoform3A in BEL-7404 human hepatoma cells and studied theeffect of p120ctn on β-catenin and E-cadherin bindingas well as p120ctn and β-catenin subcellular localizationusing immunoprecipitation,Western blotting and *** also investigated the inhibitory effectof p120ctn transfection on the expression of apoptoticprotein survivin survivin and cell cycle regulator cyclin D1in the ***:Western blotting indicated that p120ctnexpression increased after cells were transfected withp120ctn isoform *** protein was located mainlyat membrane under immunofluorescent microscope.β-catenin nuclear expression was reduced afteroverexpression of p120ctn isoform *** p120ctn-E-cadherin binding increased after transfection of p120ctnisoform ***,overexpression of p120ctndown regulated the expression of apoptotic protein sur-vivin and cell cycle regulator cyclin *** effects ledto reduction of cell ***:Our results indicate that p120ctnplays an important role in regulating the formation ofE-cadherin and-catenin complex,cell apoptosis,cellcycle and cancer cell biological function.

关键词： P120ctn β-catenin Hepatoma Cyclin D1 Survivin

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Relationship between p-catenin expression and epithelial cell proliferation in gastric mucosa with intestinal metaplasia

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World Journal of Gastroenterology 2005年第28期11卷 4400-4403页

作者： Adriana Romiti Angelo Zullo Francesco Borrini Ida Sarcina Cesare Hassan Simon Winn Silverio Tomao Aldo Vecchione Sergio Morini Pietro Mingazzini Medical Oncology "Sant'Andrea" Hospital RomeItaly Gastroenterology and Digestive Endoscopy "Nuovo Regina Margherita" Hospital RomeItaly Department of Experimental Medicine and Pathology "La Sapienza" University RomeItaly Medical Oncology "Sant" Andrea" Hospital RomeItaly Oncology IRCCS "Regina Elena" RomeItaly Co-first-authors: Adriana Romiti and Angelo Zullo

AIM： To investigate β-catenin expression in patients with intestinal metaplasia, and to look for a possible relationship between β-catenin expression and either epithelial proliferation values or Helicobacter pylori （ H pylori） infection.METHODS： Twenty patients with complete type intestinal metaplasia were studied. β-catenin expression and epithelial cell proliferation in antral mucosa were assessed using an immunohistochemical analysis. H pylori infection was detected by histology and a rapid urease test.RESULTS： Reduced β-catenin expression on the surface of metaplastic cells was detected in 13 （65%） out of 20 patients. Moreover, in eight （40%） patients intranuclear expression of β-catenin was found. When patients were analyzed according to H pylori infection, the prevalence of both β-catenin reduction at the cell surface and its intranuclear localization did not significantly differ between infected and uninfected patients. Cell proliferation was higher in patients with intranuclear β-catenin expression as compared to the remaining patients, although the difference failed to reach the statistical significance （36±8.9 vs 27.2±11.4, P= 0.06）. On the contrary, a similar cell proliferation value was observed between patients with reduced expression of β-catenin on cell surface and those with a normal expression （28.1±11.8 vs 26.1±8.8, P= 0.7）.H pylori infection significantly increased cell proliferation （33.3±10.2% vs 24.6±7.4% , respectively, P= 0.04）.CONCLUSION： Both cell surface reduction and intranuclear accumulation of β-catenin were detected in intestinal metaplasia. The intranuclear localization of β-catenin increases cell proliferation. H pylori infection does not seem to play a direct role in β-catenin alterations, whilst it significantly increases cell proliferation.

关键词： β-catenin Intestinal metaplasia Proliferation Helicobacter pylori

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Pigmented well-differentiated hepatocellular neoplasm with β-catenin mutation

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Hepatobiliary & Pancreatic Diseases International 2015年第6期14卷 660-664页

作者： Lara Neves Souza Rodrigo Bronze de Martino Richard Thompson Sandra Strautnieks Nigel D Heaton Alberto Quaglia Institute of Liver Studies King's College Hospital Department of Gastroenterology Discipline of Liver and Gastrointestinal TransplantationHospital das ClínicasUniversity of S?o Paulo

ABSTRACT： According to the most recent WHO classification of hepatocellular adenomas, a small percentage of inflammatory hepatocellular adenomas presents with mutation in the β-catenin gene and are at higher risk of malignant transformation. It has been recognized that adenoma-like hepatocellular neoplasms with focal atypia, or in unusual clinical context present with similar cytogenetic and immunohistochemistry characteristics to well-differentiated hepatocellular carcino- mas.

关键词： hepatocellular adenoma hepatocellular carcinoma β-catenin glutamine synthetase diethylstilbestrol

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Inhibitory effect of caffeic acid phenethyl ester on the growth of SW480 colorectal tumor cells involvesβ-catenin associated signaling pathway down-regulation

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World Journal of Gastroenterology 2006年第31期12卷 4981-4985页

作者： Yu-Jun He Bao-Hua Liu De-Bing Xiang Zuo-Yi Qiao Tao Fu Yu-Hong He Department of General Surgery Daping Hospital and Research Institute of Surgery Third Military Medical University Chongqing 400042 China Cancer Center Daping Hospital and Research Institute of Surgery Third Military Medical University Chongqing 400042 China Urology Center Chongqing Peace Hospital Chongqing 400020 China

AIM： To study the anti-tumor effect of caffeic acid phenethyl ester （CAPE） and the influence of CAPE on β-catenin associated signaling pathway in SW480 colorectal cancer （CRC） cells. METHODS： SW480 cells were treated with CAPE at serial concentrations. The proliferative status of cells was measured by methabenzthiazuron （MTT） assay. Cell cycle and cell apoptosis were analyzed using flow cytometry （FCM）. Western blotting assay was used to evaluate the protein level of β-catenin, c-myc and cyclinD1. β-catenin localization was determined by indirect immunofluorescence. RESULTS： CAPE displayed a strong inhibitory effect in a significant dose- and time-dependent manner on SW480 cell growth. FCM analysis showed that the ratio of G0/G1 phase cells increased, S phase ratio decreased and apoptosis rate increased after SW480 cells were exposed to CAPE for 24 h. Pretreatment of SW480 cells with CAPE significantly suppressed β-catenin, c-myc and cyclinD1 protein expression. CAPE treatment was associated with decreased accumulation of β-catenin protein in nucleus and cytoplasm, and concurrently increased its accumulation on the surface of cell membrane. CONCLUSION： CAPE can inhibit SW480 cell proliferation by inducing cell cycle arrest and apoptosis. Decreased β-catenin and the associated signaling pathway target gene expression may mediate the anti-tumor effects of CAPE.

关键词： Caffeic acid phenethyl ester Colorectal cancer Proliferation β-catenin Signaling pathway

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β-catenin、CMTM6和PD-L1蛋白在结直肠癌组织表达的相关性及临床意义

β-catenin、CMTM6和PD-L1蛋白在结直肠癌组织表达的相关性及临床...

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作者：李炳权广州医科大学

学位级别：硕士

目的WNT/β-catenin通路信号异常发生在大多数结直肠癌(Colorectal cancer,CRC),CMTM6是PD-L1表达的主要调控因子。探讨β-catenin、CMTM6和PD-L1蛋白在结直肠癌组织中的表达及临床意义。方法1、建立结直肠癌组织芯片库,收集临床病理资... 详细信息

目的WNT/β-catenin通路信号异常发生在大多数结直肠癌(Colorectal cancer,CRC),CMTM6是PD-L1表达的主要调控因子。探讨β-catenin、CMTM6和PD-L1蛋白在结直肠癌组织中的表达及临床意义。方法1、建立结直肠癌组织芯片库,收集临床病理资料并进行术后随访。2、使用免疫组化方法检测结直肠癌组织β-catenin、CMTM6、PD-L1(SP142)及PD-L1(IHC411)蛋白表达。3、结合临床病理资料及术后随访结果,探讨β-catenin、CMTM6及PD-L1蛋白表达的相关性及临床意义。结果一、PD-L1、CMTM6和β-catenin蛋白表达状况1、781例CRC组织中PD-L1(SP142)及PD-L1(IHC411)蛋白呈肿瘤细胞(Tumor Cells,TC)或肿瘤浸润性免疫细胞(Tumor-infiltrating Immune Cells,IC)均阳性表达或均阴性表达者共有704例,其中PD-L1(SP142)及PD-L1(IHC411)在肿瘤细胞均阳性表达率为11.36%(80/704),在肿瘤浸润性免疫细胞均阳性表达率为29.26%(206/704)。2、β-catenin蛋白在704例结直肠癌组织中高表达率为61.8%(435/704)。3、CMTM6蛋白在704例结直肠癌组织中阳性表达率为26.3%(185/704)。二、PD-L1、CMTM6、β-catenin蛋白表达与临床病理特征的关系。1、PD-L1在TC的阳性表达与年轻CRC患者、右半结肠、d MMR状态及CMTM6表达相关,PD-L1在TC中的表达与CRC组织学亚型、组织学分级、淋巴转移、TNM分期和β-catenin的表达未见显著相关性。2、PD-L1在IC的阳性表达与CRC组织学亚型、β-catenin高表达和CMTM6表达相关,PD-L1在IC中的表达与年龄、性别、肿瘤部位、组织学分级、淋巴结转移及MMR状态未见显著相关性,此外,PD-L1在IC的表达与TNM分期存在相关趋势(p=0.053)。3、CMTM6在CRC组织中的阳性表达与p MMR状态、β-catenin和PD-L1TC和IC表达相关,CMTM6在CRC的表达与年龄、性别、肿瘤部位、组织学亚型、组织学分级、淋巴结转移和TNM分期未见显著相关性。4、β-catenin在CRC组织中的表达与肿瘤部位、组织学亚型、组织学分级、MMR状态、PD-L1中IC的表达及CMTM6的表达相关,β-catenin在CRC组织中的表达与年龄、性别、淋巴结转移和TNM分期未见显著相关性。三、PD-L1、CMTM6、β-catenin蛋白表达与化疗及预后的关系1、术后随访5年总生存率为64.6%,单因素分析显示年龄、组织学亚型、组织学分级、淋巴结转移、TNM分期、MMR状态和PD-L1在IC中的表达与预后相关,多因素分析显示年龄、组织学分级、TNM分期、MMR状态和PD-L1在IC中的表达是影响预后的独立因素。2、在TNM III-IV期CRC患者中,化疗组的生存率明显高于非化疗组(p=0.005)。在PD-L1 TC和IC阴性表达组(p=0.023)、β-catenin高表达组(p=0.001)、CMTM6阴性表达组(p=0.018)和p MMR组(p=0.011)化疗的生存率有显著提高(p=0.041),但在PD-L1 TC和IC阳性表达组(p>0.05)、CMTM6阳性表达组(p>0.05)、β-catenin低表达组(p>0.05)和d MMR组(p>0.05)的化疗后生存率未见明显改变。结论1、PD-L1(SP142)及PD-L1(IHC411)蛋白在CRC组织的表达具有较高的一致性。2、PD-L1蛋白表达与CMTM6及β-catenin蛋白表达在CRC组织具有相关性。3、PD-L1在IC的表达、β-catenin的高表达及MMR状态与CRC患者预后密切相关。4、β-catenin、CMTM6及PD-L1蛋白表达和MMR状态可作为指导CRC患者化疗的生物标志物。

关键词：结直肠癌 PD-L1 CMTM6 β-catenin

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Sporamin suppresses growth of xenografted colorectal carcinoma in athymic BALB/c mice by inhibiting liver β-catenin and vascular endothelial growth factor expression

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World Journal of Gastroenterology 2019年第25期25卷 3196-3206页

作者： Chun Yang Jing-Jie Zhang Xiao-Peng Zhang Rong Xiao Peng-Gao Li School of Public Health Capital Medical UniversityBeijing Key Laboratory of Clinical Epidemiology

BACKGROUND Colorectal cancer(CRC)is the third most common malignancy of the digestive tract and the fifth leading cause of cancer-related mortality in ***,a Kunitz-type trypsin inhibitor isolated from sweet potato,is a potential anti-cancer agent with activities against a number of malignant tumor cells in *** liver secretes a myriad of endocrine factors that may facilitate the growth and transformation of tumors in the development of *** To investigate the effects of sporamin on liver morphology and biomarkers of xenografted CRC in the liver of athymic BALB/c *** Twenty-seven male BALB/c nude mice were randomly divided into control,vehicle,and sporamin *** in the latter two groups were intraperitoneally xenografted with LoVo colorectal carcinoma cells and intragastrically infused with saline or sporamin(0.5 g/kg body weight/d),respectively,for 3 *** and eosin(HE)staining of the sections was performed to observe morphological changes in hepatic tissue and real-time fluorescent quantitative PCR(qPCR)and enzyme-linked immunosorbent assay(ELISA)were used to measure the expression ofβ-catenin and vascular endothelial growth factor(VEGF)in the *** Sporamin significantly reduced the number and weight of tumor nodules formed in the abdominal *** with the vehicle group,the mean tumor weight(±SD)in the sporamin group was significantly reduced(0.44±0.10 g vs 0.26±0.15 g)and the total number of tumors decreased from 93 to *** staining showed that enlargement of the nucleus and synthesis of proteins within hepatocytes,as well as infiltration of inflammatory cells into the liver,were attenuated by *** staining and ELISA showed that the concentrations ofβ-catenin and VEGF in the liver were significantly reduced by *** with the vehicle group,the expression ofβ-catenin measured in integrated optical density units per area was reduced in the sporamin group(47.29±9.10 vs 26

关键词： Sporamin Colorectal cancer Liver Vascular endothelial growth factor β-catenin

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β-catenin、Runx2在腰椎间盘髓核组织中的表达及意义

β-catenin、Runx2在腰椎间盘髓核组织中的表达及意义

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作者：余雷遵义医科大学

学位级别：硕士

目的:本课题通过检测Runx2、β-catenin及Ⅱ型胶原蛋白在不同退变程度的腰椎间盘髓核(NP)组织中的表达情况,旨在重点探讨Runx2、β-catenin与腰椎间盘退变程度之间的相关性。同时本课题也探讨Ⅱ型胶原蛋白与腰椎间盘退变程度的相关性。... 详细信息

目的:本课题通过检测Runx2、β-catenin及Ⅱ型胶原蛋白在不同退变程度的腰椎间盘髓核(NP)组织中的表达情况,旨在重点探讨Runx2、β-catenin与腰椎间盘退变程度之间的相关性。同时本课题也探讨Ⅱ型胶原蛋白与腰椎间盘退变程度的相关性。方法:(1)本课题收集并分析2021年12月至2022年12月在遵义医科大学第五附属(珠海)医院骨二科住院并行椎间孔镜手术治疗的腰椎间盘突出症患者的NP组织标本共计81例。(2)所有纳入患者术前均接受腰椎磁共振(MRI)检查,根据Pfirrmann影像学分级标准将纳入患者分为轻度退变组(Pfirrmann Ⅱ-Ⅲ级)共42例和重度退变组(Pfirrmann Ⅳ-Ⅴ级)共39例。(3)术前通过记录两组患者的基本信息(包括年龄、性别和病程)并同时进行体重指数(BMI)、腰痛及腿痛NRS评分、Oswestry残疾指数(ODI)的评估,研究这些评价指标与腰椎间盘退变程度之间的关系。(4)术中将收集到的NP组织标本分别进行苏木素-伊红(HE)染色、免疫组织化学(IHC)染色以及蛋白质印迹(WB)法检测Runx2、β-catenin的蛋白相对表达量,以此研究Runx2、β-catenin与腰椎间盘退变程度之间的相关性。结果:(1)IHC染色实验结果显示,Runx2在NP细胞核和细胞质中均有表达,而β-catenin则主要表达于NP细胞质中。且两者在重度退变组的阳性表达细胞数均明显多于轻度退变组。此外,结果还显示Ⅱ型胶原蛋白在NP组织的ECM中表达,轻度退变组中Ⅱ型胶原蛋白表达呈强阳性,而在重度退变组则呈弱阳性表达。(2)WB实验结果显示,在重度退变组中Runx2、β-catenin的蛋白相对表达量显著高于轻度退变组,两组之间比较差异有统计学意义(Pβ-catenin与腰椎间盘退变程度呈正相关。且Runx2与β-catenin表达呈明显正相关。(3)在本次研究中发现,不同分组之间患者的年龄、性别构成比较差异有统计学意义(P0.05)。结论:Runx2、β-catenin表达与腰椎间盘退变程度呈正相关,而Ⅱ型胶原蛋白表达与腰椎间盘退变程度呈负相关。本研究进一步阐明,Runx2、β-catenin可能在腰椎间盘退变过程中发挥一定的作用。

关键词： Runx2 β-catenin Ⅱ型胶原蛋白腰椎间盘退变腰椎间盘突出症

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Influence of β-catenin Small Interfering RNA on Human Osteosarcoma Cells

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Journal of Huazhong University of Science and Technology(Medical Sciences) 2011年第3期31卷 353-358页

作者：张帆陈安民陈剑锋余天郭风劲 Department of Orthopedics Tongji HospitalTongji Medical CollegeHuazhong University of Science and Technology Wuhan Aier Eye Hospital

This study examined the effect of small interfering RNA-mediated β-catenin knockdown on the survival,invasion and chemosensitivity of human osteosarcoma cells（U2-OS cells）.The siRNA against β-catenin was constructed and transfected into U2-OS *** expression of β-catenin was detected by qRT-PCR and Western *** growth and apoptosis was detected in the presence or absence of doxorubicin by MTT and flow cytometry,*** invasion ability was measured by transwell *** results showed that the transfection of β-catenin siRNA resulted in decreased expression of β-catenin,suppression of invasion and motility of U2-OS cells,reduced chemosensitivity to doxorubicin in vitro,and little change in cell growth and ***,down-regulated MT1-MMP expression was found after *** was concluded that knockdown of β-catenin gene may decrease the invasive ability of human osteosarcoma cells through down-regulated MT1-MMP expression,and the chemosensitivity of osteosarcoma cells against doxorubicin.

关键词： β-catenin osteosarcoma siRNA gene therapy

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TLN1通过激活β-catenin信号通路负性调控骨髓间充质干细胞的成脂分化

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中国组织工程研究 2023年第10期27卷 1578-1583页

作者：黄红颜柯皓腾叶伟佳邓华宗王涛蔡明希陈奇凡岑水忠南方医科大学珠江医院乳腺外科广东省广州市510280 南方医科大学珠江医院脊柱外科广东省广州市510280

背景:骨髓间充质干细胞成骨-成脂分化平衡在骨代谢疾病中发挥关键作用,课题组前期研究证实TLN1可调控骨髓间充质干细胞成骨分化,但其对骨髓间充质干细胞成脂分化的作用仍未明确。目的:探讨TLN1在骨髓间充质干细胞成脂分化中的作用及机... 详细信息

背景:骨髓间充质干细胞成骨-成脂分化平衡在骨代谢疾病中发挥关键作用,课题组前期研究证实TLN1可调控骨髓间充质干细胞成骨分化,但其对骨髓间充质干细胞成脂分化的作用仍未明确。目的:探讨TLN1在骨髓间充质干细胞成脂分化中的作用及机制。方法:诱导骨髓间充质干细胞成脂分化并使用Western blot及qRT-PCR检测TLN1的表达变化;采用CCK-8检测TLN1敲减后骨髓间充质干细胞增殖能力变化,成脂诱导后进行油红O染色及定量分析,qRT-PCR检测骨髓间充质干细胞成脂分化的关键分子PPAR-γ、C/EBP-α的基因表达水平;Western blot检测成脂经典通路蛋白的表达,同时在敲减TLN1的同时添加β-catenin激活剂后检测骨髓间充质干细胞的成脂分化能力,以探讨TLN1调节成脂分化的具体分子机制。结果与结论:TLN1在骨髓间充质干细胞的成脂分化过程中表达下调;敲减TLN1对骨髓间充质干细胞的增殖无明显影响,可显著增强骨髓间充质干细胞成脂诱导分化能力;敲减TLN1可抑制活性的β-catenin表达,而激活β-catenin信号通路可逆转TLN1敲减介导的成脂分化增强。结果表明,TLN1表达在骨髓间充质干细胞成脂分化过程中逐渐下调,敲减TLN1通过抑制β-catenin信号通路发挥促进骨髓间充质干细胞成脂分化的作用。

关键词：间充质干细胞 TLN1 成脂分化 β-catenin 信号通路组织工程

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