• 한국자기공명학회논문지
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• 제21권2호
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• pp.72-77
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• 2017

${\beta}-catenin$ is a key signaling protein which regulates cell signaling and gene transcription. Abnormal activation of ${\beta}-catenin$ is linked to many cancers, particularly with colorectal cancers. Although many genetic and biological studies on $Wnt/{\beta}-catenin$ have been reported and structures of the complex between ${\beta}-catenin$ and its diverse binding partners have been published, many of them have focused on armadillo repeat domain of ${\beta}-catenin$. Both N- and C-terminal domains have been suggested to regulate interactions of ${\beta}-catenin$ with other molecules, but still little is known about the C-terminal unstructured domain. To investigate the structure of this domain, construct of C-terminus was designed and structural studies were performed using size exclusion chromatography (SEC), circular dichroism (CD), fluorescence and nuclear magnetic resonance (NMR) spectroscopy. We observed that not only the purified full-length construct but the purified C-terminal construct also dimerizes in solution by SEC, suggesting that this domain involves in dimerization of ${\beta}-catenin$. CD and fluorescence data indicate its flexibility and structural formation in the presence of membrane environments.

• Childhood Kidney Diseases
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• 제15권2호
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• pp.138-145
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• 2011

목적 : 단백뇨 질환의 실험모델인 puromycin aminonucleoside (PAN)에서 관찰할 수 있는 족세포의 병리학적 이상에 있어서 ${\beta}$-catenin의 변화를 생체 외 족세포 배양실험을 통하여 알아보고자 하였다. 방법: PAN에 의한 족세포의 ${\beta}$-catenin의 변화를 생체 외 배양실험을 통해 알아보고자 백서 사구체 상피세포를 배양하여 다양한 농도의 PAN을 투여하여 confocal 현미경을 통하여 ${\beta}$-catenin의 분포를 관찰하였고, Western blotting과 RT-PCR을 사용하여 ${\beta}$-catenin 발현의 변화를 관찰하였다. 결과:외곽세포질에 분포하는 ${\beta}$-catenin이 단일세포 혹은 응집환경에서 PAN의 농도가 올라갈수록 흐려지면서 세포간에 간극이 생기는 것을 볼 수 있었다. Western 분석에서, ${\beta}$-catenin 단백양은 PAN의 농도가 증가할수록, 특히, 고농도인 $50{\mu}g/mL$에서 24시간과 48시간이 노출 조건에서 각각 34.9%와 34.3%의 의미 있는 감소소견을 보였다(P<0.05). 이러한 소견은 RT-PCR에서도 유사하게 보였으며, 24시간에서는 고농도인$50{\mu}g/mL$ PAN을 첨가한 조건에서 25.4%의 의미 있는 감소를 보였으며, 48시간에서는 $25{\mu}g/mL$와 $50{\mu}g/mL$ PAN을 첨가한 조건에서 각각 46.6%와 51.8%의 의미 있는 감소를 보였다. 결론: PAN은 족세포에서 ${\beta}$-catenin을 세포막으로부터 내부로의 분포변화를 유발하고, ${\beta}$-cate-nin mRNA의 발현 감소와 단백수준에서 양의 감소를 초래함으로서, PAN에 의한 족세포 내 분포변화에 유전자 억제에 의한 ${\beta}$-catenin 단백의 감소로 단백뇨의 발생에 기여할 것이라 사료된다.

• 한국자원식물학회:학술대회논문집
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• 한국자원식물학회 2019년도 춘계학술대회
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• pp.92-92
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• 2019

In this study, we evaluated the effect of branch (STB) and leave (STL) extracts from Sageretia thea on ${\beta}$-catenin level in human colorecal cancer cells, SW480 and lung cancer cells, A549. STB and STL dose-dependently suppressed the growth of SW480 and A549 cells. STB and STL decreased ${\beta}$-catenin level in both protein and mRNA level. MG132 decreased the downregulation of ${\beta}$-catenin protein level induced by STB and STL. However, the inhibition of $GSK3{\beta}$ by LiCl or ROS scavenging by NAC did not block the reduction of ${\beta}$-catenin protein by STB and STL. Our results suggested that STB and STL may downregulate ${\beta}$-catenin protein level independent on $GSK3{\beta}$ and ROS. Based on these findings, STB and STL may be a potential candidate for the development of chemopreventive or therapeutic agents for human colorectal cancer and lung cancer.

• 한국임상수의학회지
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• 제26권5호
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• pp.429-432
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• 2009

Cadherin-catenin 복합체의 파괴는 ${\beta}$-catenin 단백질의 발현 위치 이상(세포내 이동)을 유발하며, 일부 receptor tyrosine kinase (RTK)의 활성화가 cadherin-catenin 복합체의 파괴를 유발할 수 있다. 본 연구에서는 ${\beta}$-catenin의 발현 위치 이상을 나타낸 개 피부 흑색종 조직 18개에서 MET/RON RTKs의 발현양을 평가하였다. 실험 결과 총 28%의 종양조직에서 MET/RON RTKs의 발현증가가 관찰되었다. 이 결과는 개 피부 흑색종에서 MET/RON RTKs의 발현증가가 ${\beta}$-catenin의 위치이상에 부분적으로 관여할 가능성을 제시한다.

• Asian Pacific Journal of Cancer Prevention
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• 제15권15호
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• pp.6103-6108
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• 2014

Many studies have reported ${\beta}$-catenin involvement in the development of esophageal carcinoma (EC), but its prognostic significance for EC patients remains controversial. Therefore, we conducted this meta-analysis to explore the issue in detail. After searching PubMed, EMBASE, Web of Science, and Chinese Biomedical Literature Database, we included a total of ten relevant studies. We pooled the overall survival (OS) data using RevMan 5.2 software. The results showed that aberrant expression of ${\beta}$-catenin was associated with a significant increase of mortality risk (hazard ratio 1.71, 95%CI 1.46-2.01; p<0.00001). Subgroup analyses further suggested that aberrant expression of ${\beta}$-catenin resulted in poor OS of EC patients regardless of histological type of EC, study location or criteria for aberrant expression of ${\beta}$-catenin, and the sensitivity analyses revealed that the result was robust. The meta-analysis revealed that aberrant expression of ${\beta}$-catenin could be a predicative factor of poor prognosis for EC patients.

• Animal cells and systems
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• 제4권4호
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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.

• Asian Pacific Journal of Cancer Prevention
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• 제15권20호
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• pp.8847-8853
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• 2014

The aim of this study was to establish the expression and localization of E-cadherin and ${\beta}$-catenin in oral squamous cell carcinomas (OSCC) so that we could correlate the findings with prognostic-relevant histopathological variables. E-cadherin and ${\beta}$-catenin expression in normal oral epithelia and in oral squamous cell carcinomas was examined immunohistochemically, and associations with histopathological differentiation and prognosis were then analyzed in 33 patients who had been operated on for OSCC. E-cadherin expression was found in (82%) of the squamous cells of well differentiated OSCC, (61%) of moderately differentiated and (39%) of poorly differentiated. E-cadherin expression was significantly associated with histological grade (p=0.000). No nuclear staining was detected. In (19.5%) of the cells E-cadherin localized in the cytoplasm, with no correlation to the histological grade (p=0.106). ${\beta}$-Catenin expression was found in 87% of the squamous cells of well differentiated OSCC, 67% of moderately differentiated and 43% of poorly differentiated, the expression was significantly associated with histological grade (p=0.000). the nuclear ${\beta}$-Catenin expression appeared in 3.3% of the cells and it was correlated to the histological grade (p=0.000). In (23.5%) of the cells ${\beta}$-Catenin localized in the cytoplasm, with correlation to the histological grade (p=0.002). According to this study the expression of ${\beta}$-catenin and E-cadherin were independent prognostic factors for histological grade. E-cadherin was closely linked to ${\beta}$-catenin expression in OSCC (p=0.000) and to tumor differentiation. That reflects a structural association and the role of both in tumor progression.

• Asian Pacific Journal of Cancer Prevention
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• 제13권12호
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• pp.6197-6201
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• 2012

Although enhancer of zeste homolog 2 (EZH2) has been reported as an independent prognostic factor in renal cell carcinoma (RCC), little is known about the exact mechanism of EZH2 in promoting the genesis of RCC. However, several studies have shown that dysregulation of the Wnt/${\beta}$-catenin signaling pathway plays a crucial role. Therefore, we determined whether EZH2 could affect ACHN human RCC cell proliferation and invasion via the Wnt/${\beta}$-catenin pathway. In the present study, we investigated the effects of short interfering RNA (siRNA)-mediated EZH2 gene silencing on Wnt/${\beta}$-catenin signaling in ACHN cells. EZH2-siRNA markedly inhibited the proliferation and invasion capabilities of ACHN, while also reducing the expression of EZH2, Wnt3a and ${\beta}$-catenin. In contrast, cellular expression of GSK-$3{\beta}$ (glycogen synthase kinase-$3{\beta}$), an inhibitor of the Wnt/${\beta}$-catenin pathway, was conspicuously higher after transfection of EZH2 siRNA. These preliminary findings suggest EZH2 may promote proliferation and invasion of ACHN cells via action on the Wnt/${\beta}$-catenin signaling pathway.

• 한국자원식물학회지
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• 제32권5호
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• pp.442-447
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• 2019

이상의 연구 결과로 미루어 볼 때, 도깨비부채 잎(RPL)은 ${\beta}-catenin$의 분해 유도를 통해 대장암, 유방암, 폐암, 전립선암 및 췌장암 세포의 생육을 억제하는 것으로 나타났다. 본 결과는 도깨비부채 잎의 항암을 위한 대체보완소재 및 천연 항암제 개발을 위한 소재로 활용이 가능할 것으로 판단된다. 그러나 추가적 연구를 통해 도깨비 부채 잎의 항암 활성물질의 분석연구가 필요할 것으로 사료된다.

• Biomolecules & Therapeutics
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• 제24권4호
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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.