06-734 Sigma-AldrichAnti-β-Catenin Antibody
Use Anti-β-Catenin Antibody (Rabbit Polyclonal Antibody) validated in ICC, IP, WB to detect β-Catenin also known as catenin (cadherin-associated protein) beta 1 (88kD).More>> Use Anti-β-Catenin Antibody (Rabbit Polyclonal Antibody) validated in ICC, IP, WB to detect β-Catenin also known as catenin (cadherin-associated protein) beta 1 (88kD). Less<<
Anti-β-Catenin Antibody MSDS (material safety data sheet) or SDS, CoA and CoQ, dossiers, brochures and other available documents.
|Species Reactivity||Key Applications||Host||Format||Antibody Type|
|H, R, M, Rb, B||ICC, IP, WB||Rb||Purified||Polyclonal Antibody|
|Presentation||Purified rabbit polyclonal IgG in buffer containing 0.1M Tris Glycine, 0.15M NaCl, 0.05% Sodium Azide, pH 7.4.|
|Safety Information according to GHS|
|Storage and Shipping Information|
|Storage Conditions||Stable for 1 year at 2-8°C from date of receipt.
Handling Recommendations: Prior to removing the cap, centrifuge the vial and gently mix the solution.
|Material Size||200 µg|
Anti-β-Catenin Antibody MSDS
Anti-β-Catenin Antibody 分析证书
|Anti-#226;-Catenin - DAM1614918||DAM1614918|
|Anti-#946;-Catenin - 2016032||2016032|
|Anti-#946;-Catenin - DAM1810813||DAM1810813|
|Anti--Catenin - 2037638||2037638|
|Anti--Catenin - 2198989||2198989|
|Anti--Catenin - 2302182||2302182|
|Anti--Catenin - DAM1588240||DAM1588240|
|Anti--Catenin - DAM1713198||DAM1713198|
|Anti--Catenin - DAM1739165||DAM1739165|
|Anti--Catenin - DAM1782775||DAM1782775|
|Fluvastatin attenuates hepatic steatosis-induced fibrogenesis in rats through inhibiting paracrine effect of hepatocyte on hepatic stellate cells.|
Chong, LW; Hsu, YC; Lee, TF; Lin, Y; Chiu, YT; Yang, KC; Wu, JC; Huang, YT
BMC gastroenterology 15 22 2015
Non-alcoholic steatohepatitis (NASH) is associated with hepatic fibrogenesis. Despite well-known cholesterol-lowering action of statins, their mechanisms against NASH-mediated fibrogenesis remain unclear. This study aimed at investigating the in vitro and in vivo anti-fibrotic properties of fluvastatin (Flu).Palmitate (PA)-induced changes in intracellular hydrogen peroxide levels in primary rat hepatocytes (PRHs) and human hepatoma cell line (HepG2) were quantified by dichlorofluorescein diacetate (DCF-DA) dye assay, whereas changes in expressions of NADPH oxidase gp91 (phox) subunit, α-smooth muscle actin (α-SMA), and NFκB p65 nuclear translocation were quantified with Western blotting. Quantitative real-time polymerase chain reaction (q-PCR) was used to investigate mRNA expressions of pro-inflammatory genes (ICAM-1, IL-6, TNF-α). Conditioned medium (CM) from PA-treated PRHs was applied to cultured rat hepatic stellate cell line, HSC-T6, with or without Flu-pretreatment for 2 h. Pro-fibrogenic gene expressions (COL1, TIMP-1, TGF-β1, α-SMA) and protein expression of α-SMA were analyzed. In vivo study using choline-deficient L-amino acid defined (CDAA) diet-induced rat NASH model was performed by randomly assigning Wistar rats (n = 28) to normal controls (n = 4), CDAA diet with vehicles, and CDAA diet with Flu (5 mg/kg or 10 mg/kg) (n = 8 each) through gavage for 4 or 8 weeks. Livers were harvested for histological, Western blot (α-SMA), and q-PCR analyses for expressions of pro-inflammatory (IL-6, iNOS, ICAM-1) and pro-fibrogenic (Col1, α-SMA, TIMP-1) genes.In vitro, Flu (1-20 μM) inhibited PA-induced free-radical production, gp91 (phox) expression, and NFκB p65 translocation in HepG2 and PRHs, while CM-induced α-SMA protein expression and pro-fibrogenic gene expressions in HSC-T6 were suppressed in Flu-pretreated cells compared to those without pretreatment. Moreover, α-SMA protein expression was significantly decreased in HSC-T6 cultured with CM from PA-Flu-treated PRHs compared to those cultured with CM from PA-treated PRHs. Flu also reduced steatosis and fibrosis scores, α-SMA protein expression, mRNA expression of pro-inflammatory and pro-fibrogenic genes in livers of CDAA rats.We demonstrated PA-induced HSC activation through paracrine effect of hepatocyte in vitro that was significantly suppressed by pre-treating HSC with Flu. In vivo, Flu alleviated steatosis-induced HSC activation and hepatic fibrogenesis through mitigating inflammation and oxidative stress, suggesting possible therapeutic role of Flu against NASH.
|The impact of low-magnitude high-frequency vibration on fracture healing is profoundly influenced by the oestrogen status in mice.|
Wehrle, E; Liedert, A; Heilmann, A; Wehner, T; Bindl, R; Fischer, L; Haffner-Luntzer, M; Jakob, F; Schinke, T; Amling, M; Ignatius, A
Disease models & mechanisms 8 93-104 2015
Fracture healing is impaired in aged and osteoporotic individuals. Because adequate mechanical stimuli are able to increase bone formation, one therapeutical approach to treat poorly healing fractures could be the application of whole-body vibration, including low-magnitude high-frequency vibration (LMHFV). We investigated the effects of LMHFV on fracture healing in aged osteoporotic mice. Female C57BL/6NCrl mice (n=96) were either ovariectomised (OVX) or sham operated (non-OVX) at age 41 weeks. When aged to 49 weeks, all mice received a femur osteotomy that was stabilised using an external fixator. The mice received whole-body vibrations (20 minutes/day) with 0.3 G: peak-to-peak acceleration and a frequency of 45 Hz. After 10 and 21 days, the osteotomised femurs and intact bones (contra-lateral femurs, lumbar spine) were evaluated using bending-testing, micro-computed tomography (μCT), histology and gene expression analyses. LMHFV disturbed fracture healing in aged non-OVX mice, with significantly reduced flexural rigidity (-81%) and bone formation (-80%) in the callus. Gene expression analyses demonstrated increased oestrogen receptor β (ERβ, encoded by Esr2) and Sost expression in the callus of the vibrated animals, but decreased β-catenin, suggesting that ERβ might mediate these negative effects through inhibition of osteoanabolic Wnt/β-catenin signalling. In contrast, in OVX mice, LMHFV significantly improved callus properties, with increased flexural rigidity (+1398%) and bone formation (+637%), which could be abolished by subcutaneous oestrogen application (0.025 mg oestrogen administered in a 90-day-release pellet). On a molecular level, we found an upregulation of ERα in the callus of the vibrated OVX mice, whereas ERβ was unaffected, indicating that ERα might mediate the osteoanabolic response. Our results indicate a major role for oestrogen in the mechanostimulation of fracture healing and imply that LMHFV might only be safe and effective in confined target populations.
|Role of TGF-β receptor III localization in polarity and breast cancer progression.|
Meyer, AE; Gatza, CE; How, T; Starr, M; Nixon, AB; Blobe, GC
Molecular biology of the cell 25 2291-304 2014
The majority of breast cancers originate from the highly polarized luminal epithelial cells lining the breast ducts. However, cell polarity is often lost during breast cancer progression. The type III transforming growth factor-β cell surface receptor (TβRIII) functions as a suppressor of breast cancer progression and also regulates the process of epithelial-to-mesenchymal transition (EMT), a consequence of which is the loss of cell polarity. Many cell surface proteins exhibit polarized expression, being targeted specifically to the apical or basolateral domains. Here we demonstrate that TβRIII is basolaterally localized in polarized breast epithelial cells and that disruption of the basolateral targeting of TβRIII through a single amino acid mutation of proline 826 in the cytosolic domain results in global loss of cell polarity through enhanced EMT. In addition, the mistargeting of TβRIII results in enhanced proliferation, migration, and invasion in vitro and enhanced tumor formation and invasion in an in vivo mouse model of breast carcinoma. These results suggest that proper localization of TβRIII is critical for maintenance of epithelial cell polarity and phenotype and expand the mechanisms by which TβRIII prevents breast cancer initiation and progression.
|Aurora kinase a suppresses metabolic stress-induced autophagic cell death by activating mTOR signaling in breast cancer cells.|
Xu, LZ; Long, ZJ; Peng, F; Liu, Y; Xu, J; Wang, C; Jiang, L; Guo, T; Kamran, M; Li, SS; Wang, CL; Wang, HJ; Zhao, YF; Wan, XY; Liu, Q
Oncotarget 5 7498-511 2014
Aberrant Aur-A signaling is associated with tumor malignant behaviors. However, its involvement in tumor metabolic stress is not fully elucidated. In the present study, prolonged nutrient deprivation was conducted into breast cancer cells to mimic metabolic stress in tumors. In these cells, autophagy was induced, leading to caspase-independent cell death, which was blocked by either targeted knockdown of autophagic gene ATG5 or autophagy inhibitor 3-Methyladenine (3-MA). Aur-A overexpression mediated resistance to autophagic cell death and promoted breast cancer cells survival when exposed to metabolic stress. Moreover, we provided evidence that Aur-A suppressed autophagy in a kinase-dependent manner. Furthermore, we revealed that Aur-A overexpression enhanced the mammalian target of rapamycin (mTOR) activity under metabolic stress by inhibiting glycogen synthase kinase 3β (GSK3β). Inhibition of mTOR activity by rapamycin sensitized Aur-A-overexpressed breast cancer cells to metabolic stress-induced cell death. Consistently, we presented an inverse correlation between Aur-A expression (high) and autophagic levels (low) in clinical breast cancer samples. In conclusion, our data provided a novel insight into the cyto-protective role of Aur-A against metabolic stress by suppressing autophagic cell death, which might help to develop alternative cell death avenues for breast cancer therapy.
|E-cadherin phosphorylation occurs during its biosynthesis to promote its cell surface stability and adhesion.|
McEwen, AE; Maher, MT; Mo, R; Gottardi, CJ
Molecular biology of the cell 25 2365-74 2014
E-cadherin is highly phosphorylated within its β-catenin-binding region, and this phosphorylation increases its affinity for β-catenin in vitro. However, the identification of key serines responsible for most cadherin phosphorylation and the adhesive consequences of modification at such serines have remained unknown. In this study, we show that as few as three serines in the β-catenin-binding domain of E-cadherin are responsible for most radioactive phosphate incorporation. These serines are required for binding to β-catenin and the mutual stability of both E-cadherin and β-catenin. Cells expressing a phosphodeficient (3Sgreater than A) E-cadherin exhibit minimal cell-cell adhesion due to enhanced endocytosis and degradation through a lysosomal compartment. Conversely, negative charge substitution at these serines (3Sgreater than D) antagonizes cadherin endocytosis and restores wild-type levels of adhesion. The cadherin kinase is membrane proximal and modifies the cadherin before it reaches the cell surface. Together these data suggest that E-cadherin phosphorylation is largely constitutive and integral to cadherin-catenin complex formation, surface stability, and function.
|Therapeutic effect of a TM4SF5-specific monoclonal antibody against colon cancer in a mouse model.|
Kim, YE; Kwon, S; Wu, G; Kim, D; Park, BK; Park, JA; Choi, KC; Kim, DS; Kwon, HJ; Lee, Y
Oncotarget 5 8402-15 2014
Transmembrane 4 superfamily member 5 protein (TM4SF5) is presumed to serve as a molecular target to prevent or treat hepatocellular carcinoma (HCC) and colon cancer in a mouse model. Previously, we reported the efficacy of anti-cancer peptide vaccine targeting TM4SF5. In addition, we reported an anti-proliferative effect of anti-TM4SF5 monoclonal antibody in HCC. Here, we investigated expression of TM4SF5 in 45 primary colon cancer tissues. Almost all of the colon cancer tissues expressed TM4SF5 based on immunohistochemistry using anti-TM4SF5 monoclonal antibody. The treatment of human colon cancer cells with anti-TM4SF5 antibody reduced growth of TM4SF5 expressing cells and enhanced expression of E-cadherin and β-catenin. Using mouse colon cancer models, we then evaluated the in vivo anti-cancer effect of anti-TM4SF5 antibody. Injection of the antibody significantly reduced growth of tumors priorly established by subcutaneous injection of human colon cancer cells HT-29 in a xenograft setting. We obtained similar results with mouse colon cancer cell line CT-26 in an allograft setting. Therefore, we suggest that the TM4SF5-specific monoclonal antibody has a therapeutic effect against colon cancer.
|The oncogenic properties of EWS/WT1 of desmoplastic small round cell tumors are unmasked by loss of p53 in murine embryonic fibroblasts.|
Bandopadhayay, P; Jabbour, AM; Riffkin, C; Salmanidis, M; Gordon, L; Popovski, D; Rigby, L; Ashley, DM; Watkins, DN; Thomas, DM; Algar, E; Ekert, PG
BMC cancer 13 585 2013
Desmoplastic small round cell tumor (DSRCT) is characterized by the presence of a fusion protein EWS/WT1, arising from the t (11;22) (p13;q12) translocation. Here we examine the oncogenic properties of two splice variants of EWS/WT1, EWS/WT1-KTS and EWS/WT1 + KTS.We over-expressed both EWS/WT1 variants in murine embryonic fibroblasts (MEFs) of wild-type, p53+/- and p53-/- backgrounds and measured effects on cell-proliferation, anchorage-independent growth, clonogenicity after serum withdrawal, and sensitivity to cytotoxic drugs and gamma irradiation in comparison to control cells. We examined gene expression profiles in cells expressing EWS/WT1. Finally we validated our key findings in a small series of DSRCT.Neither isoform of EWS/WT1 was sufficient to transform wild-type MEFs however the oncogenic potential of both was unmasked by p53 loss. Expression of EWS/WT1 in MEFs lacking at least one allele of p53 enhanced cell-proliferation, clonogenic survival and anchorage-independent growth. EWS/WT1 expression in wild-type MEFs conferred resistance to cell-cycle arrest after irradiation and daunorubicin induced apoptosis. We show DSRCT commonly have nuclear localization of p53, and copy-number amplification of MDM2/MDMX. Expression of either isoform of EWS/WT1 induced characteristic mRNA expression profiles. Gene-set enrichment analysis demonstrated enrichment of WNT pathway signatures in MEFs expressing EWS/WT1 + KTS. Wnt-activation was validated in cell lines with over-expression of EWS/WT1 and in DSRCT.In conclusion, we show both isoforms of EWS/WT1 have oncogenic potential in MEFs with loss of p53. In addition we provide the first link between EWS/WT1 and Wnt-pathway signaling. These data provide novel insights into the function of the EWS/WT1 fusion protein which characterize DSRCT.
|The intersection of genetic and chemical genomic screens identifies GSK-3α as a target in human acute myeloid leukemia.|
Versha Banerji,Stacey M Frumm,Kenneth N Ross,Loretta S Li,Anna C Schinzel,Cynthia K Hahn,Rose M Kakoza,Kwan T Chow,Linda Ross,Gabriela Alexe,Nicola Tolliday,Haig Inguilizian,Ilene Galinsky,Richard M Stone,Daniel J Deangelo,Giovanni Roti,Jon C Aster,William C Hahn,Andrew L Kung,Kimberly Stegmaier
The Journal of clinical investigation 122 2012
Acute myeloid leukemia (AML) is the most common form of acute leukemia in adults. Long-term survival of patients with AML has changed little over the past decade, necessitating the identification and validation of new AML targets. Integration of genomic approaches with small-molecule and genetically based high-throughput screening holds the promise of improved discovery of candidate targets for cancer therapy. Here, we identified a role for glycogen synthase kinase 3α (GSK-3α) in AML by performing 2 independent small-molecule library screens and an shRNA screen for perturbations that induced a differentiation expression signature in AML cells. GSK-3 is a serine-threonine kinase involved in diverse cellular processes, including differentiation, signal transduction, cell cycle regulation, and proliferation. We demonstrated that specific loss of GSK-3α induced differentiation in AML by multiple measurements, including induction of gene expression signatures, morphological changes, and cell surface markers consistent with myeloid maturation. GSK-3α-specific suppression also led to impaired growth and proliferation in vitro, induction of apoptosis, loss of colony formation in methylcellulose, and anti-AML activity in vivo. Although the role of GSK-3β has been well studied in cancer development, these studies support a role for GSK-3α in AML.
|A DNA binding mutation in estrogen receptor-α leads to suppression of Wnt signaling via β-catenin destabilization in osteoblasts.|
Mödder, UI; Rudnik, V; Liu, G; Khosla, S; Monroe, DG
Journal of cellular biochemistry 113 2248-55 2012
Estrogen receptors (ERs) play vital roles in the function and remodeling of bone. Their cellular mechanisms can broadly be categorized into those involving direct DNA binding (classical) or indirect DNA binding (non-classical). The generation of non-classical ER knock-in (ERα(-/NERKI) ) mice provides a unique opportunity to define these pathways in bone. We previously demonstrated that ERα(-/NERKI) mice exhibit an osteoporotic phenotype; however, the mechanism(s) for this remain unresolved. Gene expression analyses of cortical bone from ERα(-/NERKI) mice revealed suppression of lymphoid enhancer factor-1 (Lef1), a classic Wnt-responsive transcription factor that associates with β-catenin. Since Wnt signaling is generally considered bone anabolic, this observation leads to the hypothesis that NERKI-induced suppression of Wnt signaling may contribute to the low bone mass phenotype. We generated ERα(-/NERKI) mice crossed with the Wnt-responsive TOPGAL transgenic mouse model and observed significantly less β-galactosidase activity in ERα(-/NERKI) mice, confirming suppression of Wnt activity in vivo. Adenoviral expression of the NERKI receptor using an in vitro cell system resulted in the induction of several secreted antagonists of Wnt signaling. Furthermore, expression of NERKI abrogated Wnt10b-dependent Wnt activation using a lentiviral-mediated reporter assay. Finally, expression of NERKI destabilized β-catenin cellular protein levels and disrupted ER/β-catenin interactions. Collectively, these data suggest the osteoporotic phenotype of ERα(-/NERKI) mice may involve the suppression of Lef1-mediated Wnt signaling through both the stimulation of secreted Wnt inhibitors and/or disruption of normal β-catenin function.
|Na+/H+ exchanger regulatory factor 1 (NHERF1) directly regulates osteogenesis.|
Liu, L; Alonso, V; Guo, L; Tourkova, I; Henderson, SE; Almarza, AJ; Friedman, PA; Blair, HC
The Journal of biological chemistry 287 43312-21 2012
Bone formation requires synthesis, secretion, and mineralization of matrix. Deficiencies in these processes produce bone defects. The absence of the PDZ domain protein Na(+)/H(+) exchange regulatory factor 1 (NHERF1) in mice, or its mutation in humans, causes osteomalacia believed to reflect renal phosphate wasting. We show that NHERF1 is expressed by mineralizing osteoblasts and organizes Na(+)/H(+) exchangers (NHEs) and the PTH receptor. NHERF1-null mice display reduced bone formation and wide mineralizing fronts despite elimination of phosphate wasting by dietary supplementation. Bone mass was normal, reflecting coordinated reduction of bone resorption and formation. NHERF1-null bone had decreased strength, consistent with compromised matrix quality. Mesenchymal stem cells from NHERF1-null mice showed limited osteoblast differentiation but enhanced adipocyte differentiation. PTH signaling and Na(+)/H(+) exchange were dysregulated in these cells. Osteoclast differentiation from monocytes was unaffected. Thus, NHERF1 is required for normal osteoblast differentiation and matrix synthesis. In its absence, compensatory mechanisms maintain bone mass, but bone strength is reduced.
|Protein Blotting Handbook: 6th Edition|