• 제목/요약/키워드: p53-p21 system

검색결과 125건 처리시간 0.042초

Effects of Amifostine on Apoptosis, Cell Cycle and Cytoprotection of Human Colon Cancer Cell Lines

  • Eun Ju Lee
    • 대한의생명과학회지
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    • 제29권4호
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    • pp.287-295
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    • 2023
  • Amifostine was developed to protect cells, but it is known to induce cytotoxicity and apoptosis, and the exact mechanism is unknown. In this study, we investigated how the DNA mismatch repair (MMR) system interacts with p53 to prevent apoptosis, cell cycle arrest, and cytoprotective effects induced by amifostine. HCT116 colon cancer cells sublines HCT116/p53+,HCT116/p53+, HCT116/p53-, HCT116/E6 and HCT116+ch3/E6 cells were used for evaluation. Amifostine induced G1 arrest and increased toxicity two-fold in p53- cells regardless of MMR expression. Both G1 cell cycle arrest and induction of p53 protein peaked at 24 h after the start of amifostine exposure. Both G1 cell cycle arrest and induction of p53 protein peaked at 24 h after the start of amifostine exposure. Amifostine induced the expression of p21 protein in both p53+ and p53- cells. As for apoptosis, compared to p53- cells, p53+ cells showed 3.5~4.2 times resistance to amifostine-induced apoptosis. HCT116+E6 with both p53 and MMR loss showed maximum apoptosis at 48 h, and HCT116+ch3/E6HCT116+ch3/E6 with p53 loss showed maximum apoptosis at 24 h. As a result, it was confirmed through in vitro experiments that amifostine-induced G1 cell cycle arrest and apoptosis are mediated through a pathway dependent on MMR and p53 protein.

MCF-7 인체 유방암 세포에서 옻나무 추출물이 p53-Dependent G1 Cell Cycle에 미치는 영향 (Induction of p53-Dependent G1 Cell Cycle Arrest by Rhus verniciflua. Stokes Extract in Human Breast Carcinoma MCF-7 Cells)

  • 홍상훈;한민호;최영현;박상은
    • 대한한방내과학회지
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    • 제36권1호
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    • pp.13-21
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    • 2015
  • Objectives : In Korea, Rhus verniciflua Stokes (RVS) has been used in traditional medicine for various diseases such as back pain, syndromes of the blood system in women, gastrointestinal disease, and cancer. However, the molecular mechanisms of its anti-cancer activity have not been clearly elucidated yet. Methods : This study investigated the possible mechanisms by which RVS extract (RVE) exerts its anti-proliferative action in cultured human breast carcinoma MCF-7 cells. Results : Treatment with RVE in MCF-7 cells resulted in inhibition of cell viability through G1 arrest of the cell cycle and induction of apoptosis in a time- and concentration-dependent manner, as determined by MTT assay and flow cytometry analysis. The induction of G1 arrest by RVE treatment was associated with the inhibition of cyclin D1, cyclin-dependent kinase (Cdk) 2, retinoblastoma protein (pRB), and mouse double minute 2 (MDM2) expression. Moreover, RVE treatment concentration dependently increased the levels of tumor suppressor p53, which was associated with the marked induction of Cdk inhibitors such as p21 (Waf1/Cip1) and p27 (Kip1). However, the inhibition of p53 function by the wild-type p53-specific inhibitor, pifithrin-α, abolished the above-mentioned effects of RVE, showing that p53 was responsible for the cytotoxicity of RVE Conclusions : These data indicate that a molecular pathway involving p53-dependent G1 cell cycle arrest plays a pivotal role in the cellular response to RVE, and demonstrate the potential applications of RVE as an anti-cancer drug for breast cancer treatment.

Interaction of Microtubule-associated Protein 1B Light Chain(MAP1B-LC1) and p53 Represses Transcriptional Activity of p53

  • Kim, Jung-Woong;Lee, So-Youn;Jeong, Mi-Hee;Jang, Sang-Min;Song, Ki-Hyun;Kim, Chul-Hong;Kim, You-Jin;Choi, Kyung-Hee
    • Animal cells and systems
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    • 제12권2호
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    • pp.69-75
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    • 2008
  • The tumor suppressor and transcription factor p53 is a key modulator of cellular stress responses, and can trigger apoptosis in many cell types including neurons. In this study, we have shown that Microtubule-associated protein 1B(MAP1B) light chain interacts with tumor suppressor p53. MAP1B is one of the major cytoskeletal proteins in the developing nervous system and essential in forming axons during elongation. We also demonstrate that both p53 and MAP1B-LC1 interact in the nucleus in HEK 293 cells. Indeed, we show that the MAP1B-LC1 negatively regulates p53-dependent transcriptional activity of a reporter containing the p21 promoter. Consequently, MAP1B light chain binds with p53 and their interaction leads to the inhibition of doxorubicin-induced apoptosis in HEK 293 cells. Furthermore, these examinations might be taken into consideration when knock-down of MAP1B-LC1 is used as a cancer therapeutic strategy to enhance p53's apoptotic activity in chemotherapy.

동계 마우스 종양의 방사선 감수성 예측인자로서의 생물학적 표지자 (Biological Markers as Predictors of Radiosensitivity in Syngeneic Murine Tumors)

  • 장세경;김성희;신현수;성진실
    • Radiation Oncology Journal
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    • 제24권2호
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    • pp.128-137
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    • 2006
  • 목적: 방사선 감수성이 다양한 동계(syngeneic) 마우스 종양들을 대상으로 50% 종양억제선량과 종양성장지연 등 방사선 감수성을 대변하는 지표와 방사선에 의해 유도되는 아포토시스 간에 상관관계가 있는지 여부를 알아보고자 하였다. 또한 아포토시스와 관련된 여러 유전물질의 기본(constitutive) 발현수준을 측정한 후 이들 상호 간의 상관관계를 분석하여 방사선 감수성을 예측할 수 있는 생물학적 표지자를 알아보고자 하였다. 대상 및 방법: 동계 마우스 종양으로는 난소암 OCa-1, 유방암 MCa-K, 편평상피세포암 SCC-VII, 섬유육종 FSa-II, 간암 HCa-1을 사용하였고 이들은 PCR-SSCP 검사상 p53이 모두 자연형인 종양들이었고 주령 $8{\sim}10$ 주인 C3H/HeJ 웅성 마우스를 사용하였다. 50% 종양억제선량과 종양성장지연 및 방사선에 의해 유도되는 아포토시스를 측정하여 이들과 방사선에 의해 유도되는 아포토시스간의 상관관계를 분석하여 방사선에 의해 유도되는 아포토시스로 방사선 감수성을 예측할 수 있는지 여부를 알아보고, 또한 아포토시스와 관련된 유전물질 $053,\;p21^{WAF1/CIP1},\;BAX,\;Bcl-2,\;Bcl-x_L,\;Bcl-X_s,\;p34$ 등의 기본 발현양상 및 발현수준을 Western blot과 농도계측기로 측정한 후 이들 상호 간의 상관관계를 분석하였다. 결과: 방사선에 의해 유도된 아포토시스의 정도와 종양성장지연과의 사이에는 통계적으로 유의한 상관관계가 존재하였다(R=0.922, p=0.026). 50% 종양억제선량과의 사이에는 통계적 유의성은 변연수준이었으나(p=0.070) 상관관계의 경향을 보였다(R=-0.848). $p21^{WAF1/CIP1}$과 p34의 기본 발현수준과 50% 종양억제선량(R=0.893, p=0.041와 R=0.904, p=0.035) 및 종양성장지연(R=-0.922, p=0.026와 R=-0.890, p=0.043) 사이에는 통계적으로 유의한 상관관계가 존재하였다. 즉, $p21^{WAF1/CIP1}$과 p34의 기본 발현수준이 낮은 경우에 방사선 감수성이 높고, 기본 발현수준이 높은 경우에는 방사선 감수성이 낮은 상관관계가 존재함을 알 수 있었다. 결론: 방사선에 의해 유도된 아포토시스의 정도로 종양의 방사선 감수성을 예측하여 볼 수 있을 것으로 생각하며, 종양의 방사선 감수성을 예측할 수 있는 생물학적 표지자로 $p21^{WAF1/CIP1}$와 p34의 기본 발현수준이 이용될 수 있을 것으로 생각한다.

부레옥잠과 미나리를 이용한 연속식 하수처리에서 COD, N 및 P의 제거 (Sewage Treatment Using Water Hyacinth (Eichhornia crassipes) and Watercress (Oenanthe Javanica))

  • 박진식
    • 한국환경농학회지
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    • 제21권2호
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    • pp.144-148
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    • 2002
  • 본 연구에서는 농어촌취락배수의 효율적 처리를 위해 수생식물인 부레옥잠과, 미나리를 이용한 연속식 실험에서 유기물부하(COD)와 Total N, Total P 등을 HRT와 농도를 달리하여 제거효율을 측정하였다. 유기물(COD)의 제거효율은 HRT가 2 day인 부레옥잠조에서는 평균 50%의 제거율을 보였으며, 미나리조에서는 HRT 1.2$\sim$2 day 동안 30$\sim$50%의 제거율을 보였다. 영양염류의 제거효율은 총 질소의 경우 부레옥잠조는 약 329 kg $N/ha{\cdot}day$의 부하에서 HRT 2$\sim$3 day인 경우 40$\sim$53%가 제거되었으며, $NH_4^+-N$의 제거효율은 평균 52%로 Total N의 제거효율보다 다소 높았으며, 인은 8.2 kg $P/ha{\cdot\}day$의 부하에서 HRT 2$\sim$3 day인 경우 31$\sim$40%로 조사되었다. N 및 P 흡수율은 미나리보다 부레옥잠이 높게 나타났으며, 인의 흡수율은 질소의 흡수에 비해 낫게 조사되었다.

Snail Promotes Cancer Cell Proliferation via Its Interaction with the BIRC3

  • Rho, Seung Bae;Byun, Hyun-Jung;Kim, Boh-Ram;Lee, Chang Hoon
    • Biomolecules & Therapeutics
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    • 제30권4호
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    • pp.380-388
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    • 2022
  • Snail is implicated in tumour growth and metastasis and is up-regulated in various human tumours. Although the role of Snails in epithelial-mesenchymal transition, which is particularly important in cancer metastasis, is well known, how they regulate tumour growth is poorly described. In this study, the possible molecular mechanisms of Snail in tumour growth were explored. Baculoviral inhibitor of apoptosis protein (IAP) repeat-containing protein 3 (BIRC3), a co-activator of cell proliferation during tumourigenesis, was identified as a Snail-binding protein via a yeast two-hybrid system. Since BIRC3 is important for cell survival, the effect of BIRC3 binding partner Snail on cell survival was investigated in ovarian cancer cell lines. Results revealed that Bax expression was activated, while the expression levels of anti-apoptotic proteins were markedly decreased by small interfering RNA (siRNA) specific for Snail (siSnail). siSnail, the binding partner of siBIRC3, activated the tumour suppressor function of p53 by promoting p53 protein stability. Conversely, BIRC3 could interact with Snail, for this reason, the possibility of BIRC3 involvement in EMT was investigated. BIRC3 overexpression resulted in a decreased expression of the epithelial marker and an increased expression of the mesenchymal markers. siSnail or siBIRC3 reduced the mRNA levels of matrix metalloproteinase (MMP)-2 and MMP-9. These results provide evidence that Snail promotes cell proliferation by interacting with BIRC3 and that BIRC3 might be involved in EMT via binding to Snail in ovarian cancer cells. Therefore, our results suggested the novel relevance of BIRC3, the binding partner of Snail, in ovarian cancer development.

Application of Water Quality Management System of Freshwater Lake

  • Kim, Sun-Joo;Kim, Phil-Shik;Lee, Joo-Young
    • 한국농공학회지
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    • 제45권7호
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    • pp.38-48
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    • 2003
  • Lake water quality assessment information is useful to anyone involved in lake management, from lake owners to lake associations. It provides lake water quality criteria, which can improve the ways how to manage out lake resources and how to measure current conditions. It also provides a knowledge base so that the lakes can be protected and restored. Here, the Freshwater Lake Water Quality Management System(FLAQUM) was developed. The results of FLAQUM application by scenario proved that pollutant load at rainfall by the nonpoint sources was much more than normal times at rainfall. From the result of Scenario I (pollutant source increase case), the concentrations of Boryeong freshwater lake were BOD 9.43mg/L, T-N 4.53 mg/L and T-P 0.21 mg/L, respectively, and those values exceed the standard of agricultural water. And in case of Scenario I and II(the present case) excluding Scenario III (pollutant source decrease case), all of T-N and T-P are either mesotrophication or eutrophication, on the other hand when 60% of pollution source is removed, the concentrations of Scenario III were BOD 3.21 mg/L, T-N 0.95 mg/L, T-P 0.11 mg/L, respectively, and which satisfies the standard of agricultural water quality.

노랑꽃창포 자유수면습지의 계절에 따른 질소제거 비교 (Comparison of Seasonal Nitrogen Removal by Free-Water Surface Wetlands Planted with Iris pseudacorus L.)

  • 양홍모
    • 한국환경복원기술학회지
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    • 제14권1호
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    • pp.121-132
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    • 2011
  • Removal rates of $NO_3$-N and TN in the free-water surface wetland system during winter; December, January, February and March, spring and fall; April, May, October and November, and summer; Jun, July, August and September were investigated. The system was established on floodplain in the downstream reach of the Gwangju Stream in 2008. It measures 50 meters in length and 5.5 meters in width. Iris pseudacorus L. grown in pots for about two years were planted in the system. The water stream was funneled in by gravity and its effluent was discharged back in. Volumes and water quality of inflow and outflow were analyzed from December 2008 to November 2010. The inflow was averaged approximately 350 $m^3/day$ and hydraulic residence time was about 3 hours. Average influent and effluent $NO_3$-N concentration was 3.75 and 3.35 mg/L, respectively and $NO_3$-N retention was amounted to 10.6%. Influent and effluent TN concentration were averaged 4.93 and 4.30 mg/L, respectively and TN abatement reached to 12.9%. One-way ANOVA statistics claimed that the average removal rates of $NO_3$-N and TN during winter, spring and fall, and summer were not always the same (p<0.001). The t-Tests of three pairs among $NO_3$-N removal rates of winter, spring and fall, and summer illustrated that the removal rates of winter ($5.04{\pm}1.94$), spring and fall ($10.53{\pm}2.24$), and summer ($18.61{\pm}2.26$) were significantly different each others (p<0.001). Among TN removal rates, the three pairs of t-Tests of three seasons showed that the removal rates of winter ($5.21{\pm}2.51$), spring and fall ($11.71{\pm}3.12$), and summer ($21.53{\pm}4.86$) were significantly different from each others (p<0.001).

간호대학생의 임상실습 동안 적용한 SBAR 보고교육이 의사소통명 확성, 의사소통만족도, 보고자신감과 의사소통능력에 미치는 효과 (The Effects of SBAR Report Education on Communication Clarity, Communication Satisfaction, Reporting Confidence and Communication competency in Clinical Practice of Nursing Students)

  • 정애화;김지영;문미영
    • 한국응용과학기술학회지
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    • 제38권4호
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    • pp.1129-1142
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    • 2021
  • 본 연구는 간호대학생의 임상실습 동안 적용한 SBAR 보고교육이 의사소통명확성, 의사소통 만족도, 보고자신감, 의사소통능력에 미치는 영향요인을 파악하고자 실시되었다. 자료수집기간은 2019년 12월 1일부터 12월 20일까지이며 2개 대학교에서 임상실습을 6주 이상 완료한 3학년을 편의 추출하였다. 대상자 수는 SBAR 보고교육을 받은 103명과 교육을 받지 않은 113명이다. 자료분석은 SPSS 21.0 프로그램을 이용하여 t-tests, one-way ANOVA, Pearson's correlation coefficient 등으로 분석하였다. 의사소통명확성과 의사소통능력은 양의 상관관계(r=.52, p<.001)가 있었고, 보고자신감은 의사소통만족도와 양의 상관관계(r=.53, p<.001)가 있으며, 의사소통능력은 보고자신감과 양의 상관관계(r=.46, p<.001)가 있었다. 의사소통능력은 의사소통명확성(𝛽=.29, p<.001), 의사소통만족도(𝛽=.43, p<.001), 보고자신감(𝛽=.15, p=.009)이 유의한 영향요인이었으며, 설명력은 49.0%로 나타났다. 결론적으로 간호대학생에게 임상실습 중 실무능력을 파악하여 보고체계를 강화하기 위한 교육적 제도와 교수방법의 프로그램 개발이 필요하다.

Ectopic EBP2 expression enhances cyclin E1 expression and induces chromosome instability in HEK293 stable clones

  • Lee, Ming-Cheng;Hsieh, Chang-Hsun;Wei, Shu-Chen;Shen, Shu-Chen;Chen, Chiung-Nien;Wu, Vin-Cent;Chuang, Li-Ying;Hsieh, Fon-Jou;Wu, C. H. Herbert;Tsai-Wu, Jyy-Jih
    • BMB Reports
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    • 제41권10호
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    • pp.716-721
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    • 2008
  • To explore the effects of deregulated expression of the EBNA1 binding protein 2 (EBP2) on cell growth, we generated human HEK293 stable clones constitutively expressing an EBP2-EGFP fusion protein. We found both RNA and protein levels of cyclin E1, a dominant oncoprotein, were elevated in the EBP2- EGFP stable clones. These findings were confirmed by flow cytometry bivariate analysis of cyclin expression versus DNA content. Moreover, the increase in p21 expression and the specific phosphorylation at Ser1981 of ATM and Ser15 of p53 were also observed in these stable clones, and these observations may explain the failure to observe an increase in Cdk2 kinase activity. In addition, after one year of passage culture, the EBP2-EGFP stable clones tended to lose 4 to 5 chromosomes per cell when compared to that of control cells. All of these findings provide a possible link between deregulated expression of EBP2 and tumor development.