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Kruppel-like factor 4 and acetylated H3 mediate selenium-induced growth inhibition and apoptosis in human esophageal squamous cell carcinoma(ESCC)

Kruppel-like factor 4 and acetylated H3 mediate selenium-ind...

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“细胞活动生命活力”——中国细胞生物学学会全体会员代表大会暨第十二次学术大会

作者： Chenfei Hu~1,Wei Zhang~1,Shun He~1,Zaozao Wang~1,Qing Xu~1,Lechuang Chen~1,Mei Liu~1,Hongxia Zhu~1, Jinfeng Bai~1,Lanping Quan~1,Ningzhi Xu~1 1.Laboratory of Cell and Molecular Biology,Cancer Institute & Cancer Hospital,Chincsc Academy of Medical Sciences & Peking Unio Medical College,Beijing 100021,PR China

KLF4,also known as gut-enriched Kru'ppel-like factor(GKLF) or epithelial zinc finger,is a member of the Kru¨ppel-like factor(KLF) family of *** regulates the expression of a number of genes essential for cell cycle progression(e.g.,cyclin D1,cyclin B1,p21/WAFl,p27/Kip1),and is intimately involved in controlling Gl-S and G2-M checkpoints following DNA *** and experimental studies suggest that selenium can reduce the risk of many *** showed that selenium inhibit cancer cell growth,blocks cell cycle progression,and induces apoptosis and *** treatment also inhibited histone deacetylase(HDAC) activity and altered histone *** aim of this study is to delineate the molecular targets underlying the anticancer action of *** chose methylseleninic acid(CH3Se02H,abbreviated to MSA) and seleno-L-methionine to perform the studies in ESCC ***4 were upregulated in mRNA and protein *** treatment also inhibited the HDAC activity and increased the level of acetylated *** inhibition and apoptosis were also *** findings indicate that KLF4 and acetylated H3 may function as the downstream effectors of MSA that mediate apoptosis in *** may be a potential HDAC inhibitor.

关键词： KLF4 Epigenetic alterations selenium apoptosis ESCC

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Tamoxifen-mediated reversible immortalization of mouse dental papilla cells

Tamoxifen-mediated reversible immortalization of mouse denta...

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“细胞活动生命活力”——中国细胞生物学学会全体会员代表大会暨第十二次学术大会

作者： Heng Lin,Huan Liu,Qin Sun,Guohua Yuan,Lu Zhang,Zhi Chen State Key Laboratory Breeding Base of Basic Science of Stomatology(Hubei-MOST) and Key Laboratory for Oral Biomedicine of Ministry of Education(KLOBM),School and Hospital of Stomatology,Wuhan University,Wuhan,China

Purpose:Reversible immortalization holds great potential for primary tissue expansion to develop cell-based therapies as well as for basic *** mouse dental papilla cells(mDPCs),as precursors of odontoblasts,are promising candidates for odontoblastic *** to their limited lifespan and low proliferation activity,however,primary mDPCs are of limited use for basic *** we explore a way to generate a tamoxifen-mediated reversible immortalization mDPCs cell ***: mDPCs were isolated from dental papilla of E18.5 mouse mandibular first *** vector carrying SV40T antigen(Tag) flanked by loxP sites was used to immortalize *** then,a Cre-ERT2 plasmid was applied to make this immortalization reversible with the aid of *** antibiotic-resistant cells were selected,expanded and *** for possible biomarkers,tumor genesis,cell proliferation and differentiation were performed with biochemical,histologic,and molecular biological ***:After transfected with Tag and Cre-ERT2,one of mDPCs clones named C6 was selected for further *** C6 showed upregulated proliferation ability and increased replicative life ***,C6 was positive for odontoblastic related marker genes and able to form mineral nodules when treated with odontoblastic induction ***,this clone didn't undergo senescence after 70 passages and did not form tumors in nude *** treating C6 with 40H-tamoxifen led to efficient proviral deletion,upregulation of odontoblastic related genes,and decreased growth rates. Conclusion:Tamoxifen-mediated reversible immortalization allows the expansion of mouse dental papilla cells,leading to large production of mDPCs that retain most tissue-specific properties.

关键词： mouse dental papilla cells reversible immortalization tamoxifen Cre odontoblast

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Egr-1 decreases adipocyte insulin sensitivity by tilting PI3K/Akt and MAPK signal balance in mice

Egr-1 decreases adipocyte insulin sensitivity by tilting PI3...

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中国细胞生物学学会全体会员代表大会暨第十二次学术大会

作者： Xiao Yu Bin Xue Chao-Jun Li Ning Shen Ming-Liang Zhang Fei-Yan Pan Chen Wang Wei-Ping Jia Chang Liu Qian Gao Xiang Gao Shanghai Clinical Center of Diabetes Zhejiang Provincial Key Lab for Technology & Application of Model Organisms School of Life Sciences Wenzhou Medical College University Park Wenzhou 325035 China Department of Endocrinology and Metabolism Shanghai Diabetes Institute Shanghai Key Laboratory of Diabetes Mellitus Shanghai Jiao Tong University Affiliated Sixth People''s Hospital Shanghai 200233 China The Jiangsu Key Laboratory for Molecular and Medical Biotechnology College of Life Sciences Nanjing Normal University Nanjing 210046 China MOE Key Laboratory of Model Animals for Disease Study Model Animal Research Center and the Medical School of Nanjing University National Resource Center for Mutant Mice.Nanjing 210061 China MOE Key Laboratory of Model Animals for Disease Study Model Animal Research Center and the Medical School of Nanjing University National Resource Center for Mutant Mice.Nanjing 210061 China

It is well-known that insulin can activate both PI3K/Akt pathway, which is responsible for glucose uptake, and MAPK pathway, which is crucial for insulin resistance *** it is unclear exactly how the two pathways coordinate to regulate insulin sensitivity upon hyperinsulinism stress of type 2 diabetes mellitus (T2DM).Here we show that an early response transcription factor Egr-1 could tilt the signaling balance by blocking PI3K/Akt signaling through PTEN and augmenting Erk/MAPK signaling through GGPPS, resulting in insulin resistance in adipocytes.

关键词： Egr-1 GGPPS insulin rsistance

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MUC1 Induces Metastasis in Esophageal Squamous Cell Carcinoma by Upregulating Matrix Metalloproteinase 13

MUC1 Induces Metastasis in Esophageal Squamous Cell Carcinom...

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中国细胞生物学学会全体会员代表大会暨第十二次学术大会

作者： Qing Ye Donald Kufe Zhugang Wang Lei Huang Zheng Yan Xiaodong Liao Yuan Li Jie Yang Jiening Sun Takeshi Kawano Xiaojin Wang Ziang Cao Department of Cardiothoracic Surgery Renji Hospital Shanghai Jiao Tong University School of Medicine Shanghai 200127 P.R.China Dana-Farber Cancer Institute Harvard Medical School Boston MA 02115 Department of Medical Genetics E-Institutes of Shanghai Universities Shanghai Jiao Tong University School of Medicine Shanghai 200025 P.R.China Department of Biostatistic Shanghai Jiao Tong University School of Medicine Shanghai 200025China

Esophagus squamous cell carcinoma (ESCC) is one of the most deadly malignances because of its high frequency of *** the associations of MUC1 with ESCC and tumor metastasis, we explored a potential role of MUC1 in ESCC *** 40 ESCC and 20 paired normal tissue specimens examined, we found a significant increase of MUC1 expression in ESCC and more importantly, that expression of MUC1 and MMP13 are strongly correlated in patients that had lymph node metastasis, Studies with cell models indicated that overexpression of MUC1 upregulates the expression of MMP13,leading to increased cell *** support of a mode of transcriptional regulation, promoter analysis revealed that MUC1 stimulates MMP13 expression through the Runx-2 binding *** link of MUC1 to cell motility was further confirmed by the finding that depletion of MUC1 resulted in reduced expression of MMP13 and cell migration, invasion and ***, the loss of cell metastatic potential was rescued by overexpression of MMP13 ***, our findings indicate that MUC1 contributes to ESCC metastasis by stimulating MMP13 expression, suggesting MUC1 as a novel diagnostic biomarker and therapeutic target in ESCC.

关键词： MUC1 MMP13 ESCC Metastasis Transcription

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NMMP displays antitumor activity through inhibition of proliferation and induction of apoptosis in human hepatocellular carcinoma cell line HepG2

NMMP displays antitumor activity through inhibition of proli...

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中国细胞生物学学会全体会员代表大会暨第十二次学术大会

作者： Xiao-GuangYang Ling-Ying Lin Yong-Li Bao Yan-Xin Huang Lu-Guo Sun Yu-Wei Zhang Chun-Lei Yu Yin Wu Yu-Xin Li Research Center of Agriculture and Medicine Gene Engineering of Ministry of Education Northeast Normal University 130024ChangChun China Research Center of Agriculture and Medicine Gene Engineering of Ministry of Education Northeast Normal University 130024ChangChun China Institute of Genetics and Cytology Northeast Normal University 130024 ChangChun China Research Center of Agriculture and Medicine Gene Engineering of Ministry of Education Northeast Normal University 130024ChangChun China National Engineering Laboratory for Druggable Gene and Protein Screening Northeast Normal University 130024 ChangChun China National Engineering Laboratory for Druggable Gene and Protein Screening Northeast Normal University 130024 ChangChun China National Engineering Laboratory for Druggable Gene and Protein Screening Northeast Normal University 130024 ChangChun China Institute of Genetics and Cytology Northeast Normal University 130024 ChangChun China

6-[(1-naphthylmethyl)sulfanyl]-9H-purine (NMMP) is a derivative of *** have demonstrated that NMMP reduced the viability of HepG2 cells but not normal hepatocytes in a timeand dose-dependent *** could arrest cell cycle in G2/M phase via the reduction of CDK4 and cyclin D1/B1 *** western blot analysis, we showed that NMMP-induced cell cycle arrest is followed by *** determine further that NMMP-induced apoptosis is accomplished by the rmitochondria-dependent activation of the caspase *** reporter assays reveal that NMMP suppresses the ERK1/2 MAPK pathway and activate p53 ***, these data suggest NMMP has antitumor activity through inhibition of proliferation and induction of apoptosis, implicating its potential therapeutic value for the treatment of Hepatocellular cancer.

关键词： NMMP antitumor proliferation apoptosis

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Gabl regulates postnatal ischemic and VEGF-induced angiogenesis via activation of the PKA-eNOS pathway

Gabl regulates postnatal ischemic and VEGF-induced angiogene...

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“细胞活动生命活力”——中国细胞生物学学会全体会员代表大会暨第十二次学术大会

作者：路瑶熊彦霍迎庆韩晶岩杨晓张荣利朱德生 Stefan Klein-Heβling 李军张小玉韩晓帆李艳丽沈兵何玉龙 Masabumi Shibuya 冯更生罗金才北京大学分子医学研究所血管生物学研究室北京大学天士力微循环中心解放军军事医学科学院

The intracellular signaling mechanisms underlying postnatal angiogenesis are incompletely *** we show that Grb-2-associated binder 1(Gab1) plays a critical role in ischemic and VEGF-induced ***-specific Gab1 knockout(EGKO) mice displayed impaired angiogenesis in the ischemic hindlimb despite normal induction of VEGF *** plugs with VEGF implanted in EGKO mice induced fewer capillaries than those in control *** vessels and endothelial cells(ECs) derived from EGKO mice were defective in vascular sprouting and tube formation induced by *** analyses revealed a substantial reduction of eNOS activation in Gab1-deficient vessels and ECs following VEGF ***,the phosphorylation of Akt,an enzyme known to promote VEGF-induced eNOS activation,was increased in Gab1-deficient vessels and ECs whereas PKA activity was significantly *** of an active form of PKA rescued VEGF-induced eNOS activation and tube formation in EGKO ***-expression of wild type or mutant Gab1 molecules in EGKO ECs revealed requirement of Gab1/Shp2 association for the activation of PKA and *** together,these results identify Gab1 as a critical upstream signaling component in VEGF-induced eNOS activation and tube formation,which is dependent on *** note,this pathway is conserved in primary human ECs for VEGF-induced eNOS activation and tube formation,suggesting considerable potential in treatment of human ischemic diseases.

关键词： VEGF Gab1

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Hedgehog signaling regulates phosphorylation and ubiquitination of Suppressor of fused

Hedgehog signaling regulates phosphorylation and ubiquitinat...

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“细胞活动生命活力”——中国细胞生物学学会全体会员代表大会暨第十二次学术大会

作者： Steven Y Cheng Department of Developmental Genetics and Center for Regenerative Medicine Nanjing Medical UniversityNanjingJiangsu 210029China

Suppressor of fused(Sufu) is an essential negative regulator in the sonic hedgehog(Shh) pathway,but it is not clear how its inhibition of Shh signaling is alleviated to allow for the activation of downstream targets. To address this issue,we examined the turnover of Sufu mediated by the ubiquitin-proteasome system,and found that Shh signaling promotes the ubiquitination of *** with this result,the level of total Sufu was found to be decreased significantly in Ptch null MEFs,in which Shh signaling is inappropriately *** analysis by mass spectrometry,we determined that the ubiquitin modification of Sufu occurs on K257,which is likely to be a key residue affecting Sufu stability as the K257R mutant of Sufu was more stable and potent as a repressor of the Gli1 transcriptional activity as well as cell growth when tested in NCI-H322M lung cancer *** further found that cAMP-dependent protein kinase A(PKA), another important negative regulator in the Shh pathway,has a strong stabilizing effect on Sufu when Sufu was co-expressed with the catalytic subunit of *** again,we identified two serine residues,S342 and S346,as the sites of PKA-mediated phosphorylation by mass spectrometry,and showed that the S342/346A double mutant of Sufu is much less stable than its wild type counterpart.S346 is a consensus GSK3 recognition site whereas S342 is a typical PKA *** data showed that phosphorylation at S342 by PKA likely follows a priming event at S346 by GSK3;it is also likely to occur in vivo as evident by the detection with a poly-clonal antibody that is capable of recognizing the endogenous S342-phosphorylated form of ***,the levels of S342-phosphorylated form of as well as the total Sufu were found to be increased significantly in Smo null MEFs,which is a reciprocal corroboration to the results obtained from Ptch null *** together,these data suggest that Shh signaling likely promotes Sufu degradation through the ubiquitin

关键词： Sufu Shh phosphorylation ubiquitination

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MiR-125b Expression Affects the Proliferation and Apoptosis of Human Glioma Cells by Targeting Bmf

MiR-125b Expression Affects the Proliferation and Apoptosis ...

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“细胞活动生命活力”——中国细胞生物学学会全体会员代表大会暨第十二次学术大会

作者： Hong-Fei Xia,Tian-Zhu He,Yi Cui,Xu Ma Reproductive and Genetic Center of National Research Institute for Family Planning,Beijing,100081

Background:MicroRNAs(miRNAs) are small noncoding RNAs whose function as modulators of gene expression is crucial for the proper control of cell *** many microRNAs were found to express in central nervous system(CNS),the role of the regulatory networks in which they are involved and their function in the pathological process of nerve cells are only just *** the present study,the possible mechanisms by which one neuronal miRNAs,miR-125b,affected the growth of nervous cells were investigated using in vitro cell line ***:The expression pattern of miR-125b in ATRA-treated human glioma cell lines was detected by Northern blotting and in situ *** effect of miR-125b on the proliferation and apoptosis of human glioma cells was analyzed by MTS assay,TUNEL and Flow cytometry *** addition,the identification of target gene of miR-125b was studied by dualluciferase activity assay and Immunoblot ***:We found differential expression of miR-125b in 1.0 uM all-trans-retinoic acid(ATRA)-treated human glioma cell ***-regulation of miR-125b partially restored cell viability and inhibited cell apoptosis in U343 cells treated by ***-regulation of miR-125b decreased human glioma cells proliferation and enhanced the sensitivity of human glioma cells to ATRA-induced *** addition,we found an inverse relationship between the expression of miR-125b and the cell apoptosis-related protein Bcl-2 modifying factor(Bmf),and miR-125b can interact with 3c-untranslated region(UTR) of ***:These findings indicate that overexpression of miR-l25b promotes human glioma cell proliferation and inhibits ATRA-induced cell apoptosis and low expression of miR-125b sensitizes cells to ATRAinduced *** may play an important role in the process of miR- 125b influencing cell apoptosis.

关键词： miR-125b Human glioma cells Proliferation Apoptosis Bmf

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Increased plasma melatonin level and mtDNA copy number and decreased mtDNA damage as biomarkers for greater opiates abstinence

Increased plasma melatonin level and mtDNA copy number and d...

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“细胞活动生命活力”——中国细胞生物学学会全体会员代表大会暨第十二次学术大会

作者： Yue-mei Feng~(1,3),Ling-Yan Su~(1,3),De-Xiang Li~2,Yi-Ping Zhang~2,Yong-Gang Yao~1 1.Key Laboratory of Animal Models and Human Disease Mechanisms of the Chinese Academy of Sciences & Yunnan Province,Kunming Institute of Zoology,Kunming,Yunnan 650223,China 2.Yunnan Police Officer Academy,Kunming,Yunnan 650223,China 3.Graduate School of the Chinese Academy of Sciences,Beijing 100039,China

Drug addiction is a very serious social problem and continues to cause enormous financial costs on society. The available treatments remain to be inadequate for the drug abusers and addiction relapse rates vary depending on the substance being ***,an improved understanding of the biological change during the process of drug abstinence will lead to more effective treatment and eventually to improve the recovery of drug *** studies have demonstrated that the endocrine and metabolism systems were actively involved in this *** is the main secretory product of the pineal gland which is known to affect drug *** also functions as a powerful antioxidant to protect mitochondria and mtDNA from the oxidative damage caused by reactive oxygen species in the central nervous *** hypothesized that the change of plasma melatonin level and alteration of mtDNA in peripheral blood could be used as biomarkers for better drug *** this study,we detected the plasma melatonin level and mtDNA copy number change and damage in 13 opiate dependent females who received drug detoxification at 0,3 and 6 *** overall pattern in the drug abusers during abstinence was compared to that of 17 matched normal *** opiate abusers had a mean age of 31.7±2.4 years and were recruited from the Kunming Compulsory Drug Detoxification *** control group had a mean age of 30±1.7 years and had no history of medical,neurological or psychiatric *** melatonin level was quantified by enzyme-linked immunosorbent assay(ELISA).Quantitative real-time PCR was used to detect mtDNA copy number change and *** melatonin level,mtDNA copy number and mtDNA damage between the normal controls and drug abusers undergoing abstinence at different time points were compared by unpaired t *** also examined the time-dependent change of plasma melatonin level, mtDNA copy number change and damage in these drug abusers during drug abst

关键词： drug addiction melatonin mtDNA copy number mtDNA damage

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Construction of Recombinant Newcastle Disease Virus for Oncolytic Therapy of Cancer

Construction of Recombinant Newcastle Disease Virus for Onco...

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“细胞活动生命活力”——中国细胞生物学学会全体会员代表大会暨第十二次学术大会

作者： Ding Wei~1,Na Sun~1,Yuan Wang~1,Gang Nan~1,Zhen Ren~2,Zhi-nan Chen~1,Huijie Bian~1 1.Cell Engineering Research Centre and Department of Cell Biology.Fourth Military Medical University 2.Department of Microbiology,Third Military Medical University

Newcastle disease virus（NDV）,a naturally oncolytic virus,is known as a potential agent for cancer ***, we constructed a reverse genetic system based on Italien strain which is an oncolytic and virulence strain of NDV. Using the reverse genetic system,two recombinant NDV carrying EGFP and firefly luciferase genes were *** the proliferation kinetic and the anti-tumor activity of recombinant viruses were evaluated in vitro and in ***:To generate the recombinant NDV,a minigenome plasmid,three helper plasmids and genome plasmid were *** complete coding sequence of EGFP or firefly luciferase was inserted into the non-coding region between HN and F *** helper plasmids and genome plasmid were co-transfected into BSR-T7/5 cells to rescue the recombinant NDV To evaluate the propagation and anti-tumor characteristics,several cell lines were infected with recombinant NDV and NDV Italien,and the viral titer and cell viability were measured in different time *** evaluate the anti-tumor activity in vivo,tumor-bearing nude mice were infected with the recombinant virus through intratumoral or intravenous injection,the exogenous gene expression were observed by living image system and the tumor volume and survival time were ***:Recombinant NDV were collected and purified at 5 day post transfection and identified by genome *** data showed the insertion of exogenous reporter gene did not affect the viral propagation efficiency,and the recombinant NDV kept the characteristics of tumor-selective replication and the sensitivity to type I interferon similar as wild-type NDV Living image showed the recombinant NDV replicated in tumor tissue of nude mice ***,the recombinant NDV prolonged the survival time of nude mice significantly by intratumoral injection（P<0.05）. Conclusion:We generated the recombinant NDV with reporter gene based on NDV Italien strain for the first time which kept the propagation pr

关键词： Newcastle disease virus Reverse genetic technology Oncolytic virus Cancer

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