• Title/Summary/Keyword: TCF4

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Transcriptional Regulation and Apoptosis Induction by Tcf/$\beta$-Catenin Complex in Various T-Cells

  • Jeong, Sunjoo;Lee, Seung-Yeon;Lee, Sun-Hee
    • Animal cells and systems
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    • v.4 no.4
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    • pp.389-394
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    • 2000
  • The Tcf-1 (1-cell factor-1) protein binds to the T-cell specific enhancer sequences and plays an architectural role in the assembly of transcriptional machinery. One of the Tcf family proteins, Tcf-4, was found to be an important regulator for colon cancer development where it activates specific genes upon binding to $\beta$-catenin following Wnt signaling. We were interested in the transcriptional regulatory activities of Tcf-1 and Tcf-4 proteins in T-cells and colon cancer cells. Transactivation assay was developed using a reporter plasmid containing luciferase gene under the control of Tcf responsive elements. Luciferase activity was determined following co-transfection of the reporter along with Tcf-1 and/or $\beta$-catenin expressing plasmids. Transcription was significantly induced by $\beta$-catenin expression in all cells. Tcf-1 by itself did not induce transcription in the mature T-cell lines, but overexpressed Tcf-1 greatly activated transcription in the immature T-cell line. In addition, transfected $\beta$-catenin induced apoptosis, but co-transfected Tcf-1 suppressed apoptosis in HEK293 cells. These results suggest that Tcf-1 and $\beta$-catenin differently regulate transcription and apoptosis.

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Screening of ${\beta}$-Catenin/TCF Transcription Factor Inhibitors in Medicinal Herb Extracts

  • Choe, Ye-Dang;Na, Byung-Jo;Park, Se-Yeon
    • The Journal of Korean Medicine
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    • v.32 no.3
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    • pp.35-43
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    • 2011
  • Objectives: This study was performed to screen target-specific inhibitors of ${\beta}$-catenin/TCF signaling whose functional activation plays an important role in early events in carcinogenesis. Methods: To investigate the activation or suppression of ${\beta}$-catenin/TCF transcription, we established a transiently transfected cell line with a constitutively active ${\beta}$-catenin mutant gene whose product is not degraded. This cell line was also co-transfected with luciferase reporter gene constructs containing either an optimized (TOPflash) or mutant (FOPflash) TCF-binding element. We investigated cytotoxic effects using a 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium salt (MTS) assay. To find effective inhibitors of ${\beta}$-catenin/TCF signaling from medicinal herbs, the crude extracts of 99 types of medicinal herbs were screened using a luciferase assay system in HEK-293 and SH-SY5y cells. Results: At a concentration of $50{\mu}g$/ml, extracts of Angelica koreanae radix, Cannabis sativa semen, Ephedrae intermedia Schrenk radix, and Vitis rotundifolia fruit showed the following inhibitory effects on ${\beta}$-catenin/TCF signaling: $40{\pm}5.6%$, $23{\pm}6.1%$, $8{\pm}5.1%$, and $22{\pm}9.8%$ in ${\beta}$-catenin-activated HEK-293 cells and $9{\pm}4.7%$, $39{\pm}8.1%$, $39{\pm}6.4%$, and $42{\pm}10.1%$ in ${\beta}$-catenin-activated SH-SY5y cells, respectively. Crude extracts of E. radix were isolated by silica gel column chromatography, and two non-polar fractions of these extracts showed inhibitory effects on ${\beta}$-catenin/TCF signaling. Conclusions: In this study, we established a transiently transfected cell line as a screening system and found that various medicinal herb extracts had inhibitory effects on ${\beta}$signaling.

Improved Conductivities of SWCNT Transparent Conducting Films on PET by Spontaneous Reduction

  • Min, Hyeong-Seop;Kim, Sang-Sik;Lee, Jeon-Guk
    • Proceedings of the Materials Research Society of Korea Conference
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    • 2011.10a
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    • pp.43.2-43.2
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    • 2011
  • Single-walled carbon nanotubes (SWCNT) are transparent in the visible and show conductivity comparable to copper, and are environmentally stable. SWCNT films have high flexibility, conductivity and transparency approaching that indium tin oxide (ITO), and can be prepared inexpensively without vacuum equipment. Transparent conducting Films (TCF) of SWCNTs has the potential to replace conventional transparent conducting oxides (TCO, e.g. ITO) in a wide variety of optoelectronic devices, energy conversion and photovoltaic industry. However, the sheet resistance of SWCNT films is still higher than ITO films. A decreased in the resistivity of SWCNT-TCFs would be beneficial for such an application. We fabricated SWCNT sheet with $KAuBr_4$ on PET substrate. Arc-discharge SWCNTs were dispersed in deionized water by adding sodum dodecyl sulfate (SDS) as surfactant and sonicated, followed by the centrifugation. The dispersed SWCNT was spray-coated on PET substrate and dried on a hotplate at $100^{\circ}C$. When the spray process was terminated, the TCF was immersed into deionized water to remove the surfactant and then it was dried on hotplate. The TCF film was then treated with AuBr4-, rinsed with deionized water and dried. The surface morphology of TCF was characterized by field emission scanning electron microscopy. The sheet resistance and optical transmission properties of the TCF were measured with a four-point probe method and a UV-visible spectrometry, respectively. $HNO_3$ treated SWCNT films with Au nano-particles have the lowest 61 ${\Omega}$/< sheet resistance in the 80% transmittance. Sheet resistance was decreased due to the increase of the hole concentration at the washed SWCNT surface by p-type doping of $AuBr_4{^-}$.

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The WNT/Ca2+ pathway promotes atrial natriuretic peptide secretion by activating protein kinase C/transforming growth factor-β activated kinase 1/activating transcription factor 2 signaling in isolated beating rat atria

  • Li, Zhi-yu;Liu, Ying;Han, Zhuo-na;Li, Xiang;Wang, Yue-ying;Cui, Xun;Zhang, Ying
    • The Korean Journal of Physiology and Pharmacology
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    • v.26 no.6
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    • pp.469-478
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    • 2022
  • WNT signaling plays an important role in cardiac development, but abnormal activity is often associated with cardiac hypertrophy, myocardial infarction, remodeling, and heart failure. The effect of WNT signaling on regulation of atrial natriuretic peptide (ANP) secretion is unclear. Therefore, the purpose of this study was to investigate the effect of Wnt agonist 1 (Wnta1) on ANP secretion and mechanical dynamics in beating rat atria. Wnta1 treatment significantly increased atrial ANP secretion and pulse pressure; these effects were blocked by U73122, an antagonist of phospholipase C. U73122 also abolished the effects of Wnta1-mediated upregulation of protein kinase C (PKC) β and γ expression, and the PKC antagonist Go 6983 eliminated Wnta1-induced secretion of ANP. In addition, Wnta1 upregulated levels of phospho-transforming growth factor-β activated kinase 1 (p-TAK1), TAK1 banding 1 (TAB1) and phospho-activating transcription factor 2 (p-ATF2); these effects were blocked by both U73122 and Go 6983. Wnta1-induced ATF2 was abrogated by inhibition of TAK1. Furthermore, Wnta1 upregulated the expression of T cell factor (TCF) 3, TCF4, and lymphoid enhancer factor 1 (LEF1), and these effects were blocked by U73122 and Go 6983. Tak1 inhibition abolished the Wnta1-induced expression of TCF3, TCF4, and LEF1 and Wnta1-mediated ANP secretion and changes in mechanical dynamics. These results suggest that Wnta1 increased the secretion of ANP and mechanical dynamics in beating rat atria by activation of PKC-TAK1-ATF2-TCF3/LEF1 and TCF4/LEF1 signaling mainly via the WNT/Ca2+ pathway. It is also suggested that WNT-ANP signaling is implicated in cardiac physiology and pathophysiology.

Influence of $TiO_2$ on the dielectric properties of $Bi(Nb_{0.7}Ta_{0.3})O_4$ ceramics for low-firing (저온소결용 $Bi(Nb_{0.7}Ta_{0.3})O_4$ 세라믹스의 유전특성에 미치는 $TiO_2$ 영향)

  • Kim, Dae-Min;Yoon, Sang-Ok;Kim, Kwan-Soo;Kim, Shin;Kim, Jae-Chan;Kim, Kyung-Joo;Park, Jong-Guk
    • Proceedings of the Korean Institute of Electrical and Electronic Material Engineers Conference
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    • 2007.06a
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    • pp.298-298
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    • 2007
  • Influence of $TiO_2$ on the dielectric properties of the $Bi(Nb_{0.7}Ta_{0.3})O_4$ ceramic with 7 wt% zinc borosilicate(ZBS) glass was investigated as a function of the $TiO_2$ contents with a view to applying this system to LTCC technology. The $Bi(Nb_{0.7}Ta_{0.3})O_4$ ceramic addition of 7 wt% ZBS glass ensured successful sintering below $900^{\circ}C$. But, TCF of $Bi(Nb_{0.7}Ta_{0.3})O_4$ ceramic is large negative values, respectively, it is necessary to adjust to zero TCF for practical applications Therefore, the addition of materials having positive TCF, such as $TiO_2$, might be an effective method for the improvement. In general, increasing addition of $TiO_2$ increased dielectric constant and TCF but it decreased the sinterability and $Q{\tiems}f$ value significantly due to the dielectric property and high sintering temperature of $TiO_2$. $Bi(Nb_{0.7}Ta_{0.3})O_4$ ceramic with 7 wt% ZBS glass and then addition 0.5 wt% $TiO_2$ sintered at $900^{\circ}C$ demonstrated 42 in the dielectric constant(${\varepsilon}_r$), 1,000 GHz in the $Q{\times}f$ value, and $10{\pm}5\;ppm/^{\circ}C$ in the temperature coefficient of resonant frequency(${\tau}_f$).

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Extract from the branches of Rhamnus yoshinoi exerts anti-cancer effects on human prostate cancer cells through Wnt/β-catenin proteasomal degradation and identification of compounds by GC/MS (짝자래나무[Rhamnus yoshinoi] 가지 추출물에 의한 전립선암세포의 Wnt/β-catenin 분해 유도 활성 및 GC/MS 분석)

  • Kang, Yeongyeong;Eo, Hyun Ji;Kim, Da Som;Park, Youngki;Park, Gwang Hun
    • Journal of Plant Biotechnology
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    • v.48 no.2
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    • pp.106-114
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    • 2021
  • We evaluated the anti-cancer activity against human prostate cancer cells and the associated molecular mechanism of extracts from the branches of Rhamnus yoshinoi (RYB). Treatment with RYB suppressed viability of human prostate cancer cells (PC-3) and decreased protein levels of both β-catenin and T-cell factor 4 (TCF4). This was reflected in reduced TCF4 mRNA, but not decreased β-catenin mRNA. PC-3 cells were pretreated with the proteosome inhibitor MG132 before treatment with RYB, which blocked RYB-mediated down regulation of β-catenin in PC-3 cells, thus confirming that RYB promotes the proteasomal degradation of β-catenin. RYB induced β-catenin phosphorylation, and GSK-3β inhibition by LiCl blocked the phosphorylation and proteasomal degradation of β-catenin by RYB. These results suggest that GSK-3β may be an important upstream kinase for RYB-mediated regulation of β-catenin. Finally, GC/MS analysis of RYB identified 18 compounds. Based on these findings, RYB shows potential for development as a therapeutic agent for prostate cancer.

Expression of the E-cadherin/β-catenin/tcf-4 Pathway in Gastric Diseases with Relation to Helicobacter pylori Infection: Clinical and Pathological Implications

  • Yu, Xiu-Wen;Xu, Qian;Xu, Ying;Gong, Yue-Hua;Yuan, Yuan
    • Asian Pacific Journal of Cancer Prevention
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    • v.15 no.1
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    • pp.215-220
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    • 2014
  • Objective: To determine the expression of E-cadherin, ${\beta}$-catenin, and transcription factor 4 (TCF4) proteins in gastric diseases with relation to Helicobacter pylori infection. Methods: A total of 309 patients including 60 with superficial gastritis (SG), 57 with atrophic gastritis (AG) and 192 with gastric cancer (GC), were enrolled. The expression of E-cadherin, ${\beta}$-catenin, TCF4 proteins in the gastric mucosa was detected by immunohistochemistry and H. pylori infection by immunohistochemistry and PCR. Results: The expression rates of E-cadherin were significantly higher in SG and AG than in GC (P<0.01), while those of ${\beta}$-catenin in the nucleus were significantly lower in SG and AG than in GC (P<0.05). In GC cases, the expression rates of E-cadherin, ${\beta}$-catenin and TCF4 were significantly higher in the intestinal type than in the diffuse type (P<0.05). In GC patients, the expression rate of E-cadherin was significantly higher in the presence of H. pylori than in the absence of infection (P=0.011). Moreover, the expression level of TCF4 and ${\beta}$-catenin protein was significantly higher in the nucleus and cytoplasm in H. pylori positive than in H. pylori negative GC patients, especially in those with the intestinal type (all P < 0.05). Conclusion: The expression of E-cadherin and ${\beta}$-catenin progressively decreases during the process of GC tumorigenesis, while overexpression of TCF4 occurs. H. pylori infection is associated with a significant increase in the expression of E-cadherin and ${\beta}$-catenin in the cytoplasm and nucleus in GC patients, especially those with the intestinal type.

Inhibitory Activity of Lonicera caerulea Against Cell Proliferation in Human Colorectal Cancer Cells (댕댕이나무(Lonicera caerulea)의 대장암세포 생육억제 활성)

  • An, Mi-Yun;Eo, Hyun Ji;Son, Ho-Jun;Park, Gwang Hun;Jeong, Jin Boo
    • Korean Journal of Plant Resources
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    • v.33 no.4
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    • pp.263-270
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    • 2020
  • In this study, we evaluated the effect of the extracts from Lonicera caerulea leaves (LCLE), branches (LCBE) and fruits (LCFE) on the cell growth and migration in human colorectal cancer cells, HCT116 and SW480 cells. LCLE and LCBE dose- and time-dependently inhibited the proliferation of HCT116 and SW480 cells. However, LCFE did not affect the proliferation of HCT116 and SW480 cells. In addition, LCLE and LCBE dramatically cell migration and wound healing in HCT116 cells. LCLE and LCBE decreased β-catenin protein level but not mRNA level in HCT116 and SW480 cells. Furthermore, LCLE decreased TCF4 level in both protein and mRNA level in HCT116 and SW480 cells. However, LCBE decreased TCF4 protein level but not mRNA level in HCT116 and SW480 cells. Based on these findings, LCLE and LCBE may inhibit the cell proliferation and migration through blocking Wnt signaling activation in human colorectal cancer cells. Therefore, LCLE and LCBE may be a potential candidate for the development of chemopreventive or therapeutic agents for human colorectal cancer.

The Cryoprotective Effect on Frozen-thawed Boar Semen of Egg Yolk Low Density Lipoproteins

  • Hu, Jian-hong;Li, Qing-Wang;Li, Gang;Chen, Xiao-Yu;Hai-Yang, Hai-Yang;Zhang, Shu-Shan;Wang, Li-Qiang
    • Asian-Australasian Journal of Animal Sciences
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    • v.19 no.4
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    • pp.486-494
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    • 2006
  • In order to protect the spermatozoa against cold shock, hen egg yolk is widely used as a cryoprotective agent in semen freezing extenders for domestic animals. The protective action of yolk is largely presumed to be due to low density lipoproteins (LDL). The effects of LDL on sperm quality of bull and northern pike (Esox lucius) after freezing-thawing have been reported, but no study has been made to evaluate the effect of LDL on boar sperm motility and other characteristics. The experiment was carried out to investigate the effect of LDL on the freezing of boar sperm in 0.25 ml straws. The aim was to evaluate the quality of boar spermatozoa cryopreserved in the presence of LDL. Motility of semen cryopreserved in LDL was analyzed and compared to semen cryopreserved with Tris-citric acid-glucose (TCG) and Tris-citric acid-fructose (TCF), two basic freezing extenders containing egg yolk. Similarly, acrosome and plasma membrane integrity were also evaluated and compared to semen cryopreserved with TCG and TCF. Analysis of sperm quality after freeze-thaw showed that the motility, acrosome and plasma membrane integrity were improved with LDL in the extender, as compared to the TCG and TCF. The highest post-thaw integrity of acrosome and plasma membrane and motility were obtained with 9% LDL (w/v). Consequently, the optimum LDL concentration in the extender was 9%. It is also suggested that the concentration of LDL addition is important for the effect on boar sperm protection during freezing and thawing. The percentage of motile spermatozoa was significantly higher after freezing in 9% LDL than in TCG and TCF 54.4% versus 30.4% and 30.1% (p<0.05), respectively. The integrity of acrosome and plasma membrane were also significantly higher at 70.3% and 50.5% respectively with semen frozen in 9% LDL extender compared to TCG at 37.8% and 30.3% and TCF at 36.4% and 29.9%, respectively (p<0.05),. In conclusion, we propose that extender containing LDL extracted from hen egg yolk could be used as a cryoprotective media with a better efficiency than TCG and TCF. LDL improved boar semen quality, allowing better spermatozoa motility, acrosome and plasma membrane integrity after the freeze-thaw process. Furthermore, we found out that the extender with 9% LDL concentration significantly enhanced motility, acrosome and plasma membrane integrity of boar sperm after freezing and thawing.

Inhibition of Wnt Signaling by Silymarin in Human Colorectal Cancer Cells

  • Eo, Hyun Ji;Park, Gwang Hun;Jeong, Jin Boo
    • Biomolecules & Therapeutics
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    • v.24 no.4
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    • pp.380-386
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    • 2016
  • Silymarin from milk thistle (Silybum marianum) has been reported to show an anti-cancer activity. In previous study, we reported that silymarin induces cyclin D1 proteasomal degradation through NF-${\kappa}B$-mediated threonine-286 phosphorylation. However, mechanism for the inhibition of Wnt signaling by silymarin still remains unanswered. Thus, we investigated whether silymarin affects Wnt signaling in human colorectal cancer cells to elucidate the additional anti-cancer mechanism of silymarin. Transient transfection with a TOP and FOP FLASH luciferase construct indicated that silymarin suppressed the transcriptional activity of ${\beta}$-catenin/TCF. Silymarin treatment resulted in a decrease of intracellular ${\beta}$-catenin protein but not mRNA. The inhibition of proteasome by MG132 and $GSK3{\beta}$ inhibition by SB216763 blocked silymarin-mediated downregulation of ${\beta}$-catenin. In addition, silymarin increased phosphorylation of ${\beta}$-catenin and a point mutation of S33Y attenuated silymarin-mediated ${\beta}$-catenin downregulation. In addition, silymarin decreased TCF4 and increased Axin expression in both protein and mRNA level. From these results, we suggest that silymarin-mediated downregulation of ${\beta}$-catenin and TCF4 may result in the inhibition of Wnt signaling in human colorectal cancer cells.