HGF/SF、c-met基因信号异常与胃肠道恶性肿瘤

癌基因的变异及其参与的信号传导与肿瘤的关系成为当今生命科学研究领域的热点领域.在细胞信号传导网络中重要的传导通路之一是酪氨酸激酶受体通路,肝细胞生长因子/离散因子(HGF/SF)和他的受体c-met:具有酪氨酸激酶活性,刺激上皮细胞增生、迁移、形态发生,与恶性肿瘤的发生、浸润、转移相关.我们就目前的相关研究论述HGF/SF、c-met和他们与胃肠道恶性肿瘤的关系进展.

肝炎病毒蛋白对肝细胞基因组转录调节及信号转导机制的影响

乙型肝炎病毒(HBV)和丙型肝炎病毒(HCV)是引起慢性病毒性肝炎的主要肝炎病毒类型,而且也是肝细胞癌(HCC)的重要病因.HBV和HCV感染肝细胞之后,表达出肝炎病毒蛋白,HBV和HCV蛋白通过与转录因子蛋白结合,或通过对于肝细胞内信号转导通路的影响,使肝细胞基因组的转录表达产生异常的调节,从而影响HCC的发生.

丙型肝炎病毒蛋白对Bcl-10蛋白信号转导的影响

0 引言初原癌基因Bcl-10是作为低度B细胞淋巴瘤(BCL,B-cell lymphoma)相关基因得到鉴定的,Bcl-10是一种含有胱冬肽酶募集结构域(caspase recruitment domain,CARD)的蛋白,同时属于黏膜相关淋巴组织(mucosa-associated lymphoidtissue,MALT)B淋巴瘤中鉴定的断裂位点的基因,在淋巴细胞中抗原受体介导的NF-κB激活过程中是必需的.Bcl-10属于CARD蛋白家族成员,调节细胞凋亡和NF-κB信号转导[1-5].初步研究结果表明,丙型肝炎病毒(HCV)基因组编码蛋白对于Bcl-10的基因表达水平具有显著的上调作用,Bcl-10基因的表达在HCV感染引起的病毒性肝炎、肝硬化和肝细胞癌(HCC)的发病机制中具有重要的作用[6].

乙型肝炎病毒对细胞信号转导的影响

0引言乙型肝炎病毒(HBV)是嗜肝DNA病毒的一种,HBVDNA长度为3.2kb,具有4个开放读码框架(ORF),分别编码HBV的表面抗原蛋白,核心/e抗原,X蛋白以及HBV DNA的聚合酶.此外,HBV DNA结构中还有4段启动子、2段增强子以及与HBV DNA复制过程密切相关的顺向重复序列1、2(DR1、DR2)等[1].

乙型肝炎病毒和丙型肝炎病毒对FAP48信号转导的影响

0 引言作为一种分子量为48 kD蛋白,FAP48是细胞内与免疫调节有密切关系的蛋白类型[1].虽然FAP48是在研究免疫抑制剂的作用机制中发现的,但是FAP48蛋白在免疫调节及临床疾病的发生、发展过程中具有十分重要的作用[2].

乙型肝炎病毒和丙型肝炎病毒对MAPKKK蛋白信号转导的影响

0 引言在真核细胞中,丝裂原活化蛋白激酶(MAPK)信号转导系统对大量的细胞内、外刺激的转导起着中枢性调节作用,从而控制细胞的生长、增生、凋亡,如进入细胞周期、控制核苷酸的生物合成、G2/M期的转变、M期高尔基体的裂解和纺缍体的形成等[1].

To investigate the regulation effect of protein kinase A on IL-6-induced STAT3 activation in myeloma cells. Methods: Two human myeloma cell lines-Sko-007 and U266 were pretreated with Forskolin, a protein kinase A antagonist, and then stimulated by IL-6. The activation state of STAT3 in these two cells were examined by electrophoretic mobility shift assay (EMSA). Results: Although PKA pathway itself doesn't participate in IL-6 signal transduction in Sko-007 and U266 cells, activation of protein kinase A can inhibit IL-6-induced STAT3 activation in these two cell lines. Conclusion: There exists an inhibitory effect of protein kinase A on STAT3 activation in human myeloma cells treated by IL-6.

Microtubule-associated protein 1B plays an important role in axon guidance and neuronal migration. In the present study, we sought to discover the mechanisms underlying microtu-bule-associated protein 1B mediation of axon guidance and neuronal migration. We exposed bone marrow mesenchymal stem cells to okadaic acid or N-acetyl-D-erythro-sphingosine (an inhibitor and stimulator, respectively, of protein phosphatase 2A) for 24 hours. The expression of the phosphorylated form of type I microtubule-associated protein 1B in the cells was greater after exposure to okadaic acid and lower after N-acetyl-D-erythro-sphingosine. We then injected the bone marrow mesenchymal stem cells through the ear vein into rabbit models of spinal cord contusion. The migration of bone marrow mesenchymal stem cells towards the injured spinal cord was poorer in cells exposed to okadaic acid-and N-acetyl-D-erythro-sphingosine than in non-treated bone marrow mesenchymal stem cells. Finally, we blocked phosphatidylinosi-tol 3-kinase (PI3K) and extracellular signal-regulated kinase 1/2 (ERK1/2) pathways in rabbit bone marrow mesenchymal stem cells using the inhibitors LY294002 and U0126, respectively. LY294002 resulted in an elevated expression of phosphorylated type I microtubule-associated protein 1B, whereas U0126 caused a reduction in expression. The present data indicate that PI3K and ERK1/2 in bone marrow mesenchymal stem cells modulate the phosphorylation of micro-tubule-associated protein 1B via a cross-signaling network, and affect the migratory efifciency of bone marrow mesenchymal stem cells towards injured spinal cord.

细胞信号转导的概念研究进展及其与危重病的临床意义

生物细胞具有极其复杂的生命活动,细胞每时每刻都在接受来自细胞内外的各种各样的信号,细胞信号转导(cell signal transduction,CST)是生命活动的一种基本主要的方式.

Mechano- Chemical Coupling at Molecular Level: Forced Dissociation of Selectin/Ligand Binding

Mechano - chemical coupling is a common phenomenon that exists in various biological processes at different physiological levels. Bone tissue remodeling strongly depends on the local mechanical load. Leukocytes are sheared to form the transient aggregates with platelets or other leukocytes in the circulation. Flow pattern affects the signal transduction pathways in endothelial cells. Receptor/ligand interactions are important to cell adhesion since they supply the physical linkages among cells. How external forces influence the biological function has little been known, and nowadays attract more and more attentions. Here the forced dissociation of selectin/ligand binding is used to test mechano - chemical coupling at molecular level.

从受体及信号转导系统的研究着手促进内分泌及代谢病研究的深入

内分泌领域的研究有100多年历史,过去的100多年内分泌学家主要研究激素及内分泌腺体,如腺体解剖及发育、激素分泌及调节、激素生化及生理功能等.经100多年的努力,对已知激素基本已经清楚.随着研究的深入,人们发现有时激素水平很高,但表现出激素缺乏的临床表现,使人们领悟到激素的生物效应不但与激素的质和量相关,与激素的反应性即受体及信号转导系统关系更密切.故研究模式逐渐转向研究受体及信号转导系统,这是一个挑战,也是一个机遇,我们应抓住机遇,迎头赶上国际发展的步伐[1].

微波辐射对细胞信号转导的影响

微波(Microwave,MW)是指频率在300MHz～300GHz的电磁辐射,是非电离辐射的一部分.微波在雷达、无线通讯、感应加热、医疗和科研等领域的应用十分广泛.以往研究表明微波辐射对生物体存在热效应(thermal effect)和非热效应(non-thermal effect).随着微波技术的日新月异,微波辐射已成为损伤人类健康的重要物理因素之一.生物体内的细胞信号转导(signal transduction)是受微波辐射影响的一个重要方面,逐渐成为国内外学者关注的焦点.

Objective:Very low density lipoprotein receptor (VLDLR) has been considered as a multiple function receptor due to binding numerous ligands, causing endocytosis and regulating cel ular signaling. Our group previously reported that type II VLDLR overexpression in breast cancer tissues. The purpose of this study is to characterize type II VLDLR activities during cel migration using breast cancer cel lines. Methods:Western blotting was used to test protein expression. Cel migration was analyzed by Scratch wound assay. The mRNA expression was tested by realtime-PCR. Reporter assay was to test the transcription activity. Results:Scratch wound and Report assay indicated up-regulated VLDLR II expression promotes cel migration via activating Wnt/β-catenin pathway. The target genes such as VEGF, MMP2 and MMP7 were upregulated in VLDLR II overexpressed cel s. On the contrary, cel s treated with TFPI had an inhibition ef ect of cel migration response to down-regulation of VLDLR II. Conclusion:Type II VLDLR conferred a migration and invasion advantage by activating Wnt/β-catenin pathway, then up-regulating VEGF, MMP2 and MMP7 in breast cancer cel s.

K离子通道在剪切力诱导血管内皮细胞信号转导中的作用

血液在血管中流动时对血管壁产生持续的作力,分为剪切力、周向应力和压应力[1],剪切力在心血管系统的许多病理及病理生理过程中起着重要而跃的作用[2],它可以影响血管内皮细胞的形态及功能,导致应激的和缓慢的组织应答.剪切力信号通过血管内皮细胞的转导主要通过细胞骨架与生化因的相互作用,并引起内皮细胞结构、代谢及基因表达的变化[3,4].但长期以来,剪切力诱导内皮细胞形态学和功能的改变未能受到足够的重视,本综述描述了剪切力信号转导的可能途径,重点是离子通道(特别是K+通道)对剪切力的应答以及由此引起的细胞反应.

肿瘤坏死因子-α致胰岛素抵抗

胰岛素抵抗(insulin resistance,IR)是指胰岛素作用的靶器官、组织(主要为肝脏、肌肉、脂肪组织)对胰岛素生物学效应的反应性降低或丧失,因而产生一系列病理和临床表现.IR的病因复杂,一般认为有关基因突变所造成的极端IR很少见,而遗传易感性基础上的环境因素可能起着重要影响,但对其产生的具体机制并不明了.近年来,肿瘤坏死因子(TNF-α)在IR发生机制中的作用受到了很大关注.本文对TNF-α与IR的关系作一简要综述.

AIM:Atherosclerosis primarily involved systemic arteries .Luminal surface , a monolayer of endothelial cells , of artery directly exposes to blood and is susceptible to active substances in the blood .Exosomes contain significantly amount of proteins and RNAs .Ex-osomes can be good and bad for cells , depending on their component .Thus, exosomes may contribute to atherosclerosis by affecting endothelial cells .This study analyzed the relationship of exosome proteins and atherosclerosis .METHODS: Fifty-six patients and healthy subjects were recruited and divided into two comparisons:healthy subjects vs atherosclerosis ( HS vs AS) , and hypertension vs hypertension plus atherosclerosis ( HT vs HT+AS) .Serum exosomes were decoded by protein mass spectrometry .The protein profile and function were analyzed by gene ontology ( GO) .RESULTS:It was found that five child terms repeatedly appeared in “response to stimulus” and “immune system process” of BP of the two categories ( HS vs AS and AS vs HT+AS):“positive regulation of innate immune response”,“immune response-activating signal transduction”,”activation of innate immune response”,“innate immune re-sponse-activating signal transduction” and “innate immune response activating cell surface receptor signaling pathway ”.Two child terms repeatedly showed in “binding” of MF of the two categories:“antigen binding” and “enzyme binding”.Two proteins, PSMA6 and PSMA7, were repeatedly shown in the two categories .CONCLUSION:GO analysis was utilized for structure hierarchy “tree” to illustrate these proteins involved in various terms in BP , CC and MF.The PPI analysis supplied proteins which may play potentially im-portant roles in AS process .Innate immune system and blood coagulation pathway contribute to AS formation .The proteins, PSMA6, PSMA7 and Annexin A2, may can be the new target proteins for prevention and treatment of AS .

1 IntroductionRecent progress in molecular biology has enabled us to better understand the molecular mechanism underlying pathogenesis of human malignancy including lung cancer. Sequencing of human genome has identified many oncogenes and tumor suppressor genes,giving us a better understanding of the molecular events leading to the formation, progression, metastasis, and the development of drug resistance in human lung cancer. In addition, many signal transduction pathways have been discovered that play important roles in lung cancer. Novel strategy of anti-cancer drug development now involves the identification and development of targeted therapy that interrupts one or more than one pathways or cross-talk among different signal transduction pathways. In addition, efforts are underway that combine the traditional cytotoxic (non-targeted) agents with the biological (targeted) therapy to increase the response rate and survival in patients with lung cancer, especially advanced non-small cell lung cancer (NSCLC).

Oestrogen is essential for maintaining bone mass, and it has been demonstrated to induce osteoblast proliferation and bone formation. In this study, complementary DNA (cDNA) microarrays were used to identify and study the expression of novel genes that may be involved in MC3T3-E1 cells’ response to 17-b estradiol. MC3T3-E1 cells were inoculated in minimum essential media alpha (a-MEM) cell culture supplemented with 17-b estradiol at different concentrations and for different time periods. MC3T3-E1 cells treated with 1028 mol?L21 17-b estradiol for 5 days exhibited the highest proliferation and alkaline phosphatase (ALP) activity;thus, this group was chosen for microarray analysis. The harvested RNA was used for microarray hybridisation and subsequent real-time reverse transcription polymerase chain reaction (RT-PCR) to validate the expression levels for selected genes. The microarray results were analysed using both functional and pathway analysis. In this study, microarray analysis detected 5 403 differentially expressed genes, of which 1 996 genes were upregulated and 3 407 genes were downregulated, 1 553 different functional classifications were identified by gene ontology (GO) analysis and 53 different pathways were involved based on pathway analysis. Among the differentially expressed genes, a portion not previously reported to be associated with the osteoblast response to oestrogen was identified. These findings clearly demonstrate that the expression of genes related to osteoblast proliferation, cell differentiation, collagens and transforming growth factor beta (TGF-b)-related cytokines increases, while the expression of genes related to apoptosis and osteoclast differentiation decreases, following the exposure of MC3T3-E1 cells to a-MEM supplemented with 17-b estradiol. Microarray analysis with functional gene classification is critical for a complete understanding of complementary intracellular processes. This microarray analysis provides large-scale gene expression data that require further confirmatory studies.

紫外线诱导皮肤肿瘤的信号转导通路研究进展

皮肤肿瘤的原因复杂,长期紫外线照射是比较明确的致癌因素.有研究发现,紫外线可导致DNA损伤、特定癌基因的激活、特定抑癌基因的失活及免疫抑制等,但其致肿瘤的具体作用机制尚不十分明确.随着肿瘤分子生物学的进展,有关细胞信号传导与肿瘤发生发展关系的研究越来越受到关注.本文就近年来关于紫外线诱导皮肤肿瘤形成的相关信号转导通路综述如下.

Objective: To study transforming growth factor-β1(TGF-β1) autoproduction in keloid fibroblasts and theregulation effect of blocking TGF-β intracellular signalingon rhTGF-β1 autoproduction.Methods: Keloid fibroblasts cultured in vitro weretreated with either rhTGF-β1 (5 ng/ml ) or recombinantadenovirus containing a truncated type II TGF-β receptorgene (50 pfu/cell ). Their effects of regulating geneexpression of TGF-β1 and its receptor I and II wereobserved with Northern blot.Results: rhTGF-β1 up-regulated the gene expressionof TGF-β1 and receptor I, but not receptor II. Over-expression of the truncated receptor II down-regulated thegene expression of TGF-β1 and its receptor I, but notreceptor II.Conclusions: TGF-β1 autoproduction was observed inkeloid fibroblasts. Over-expression of the truncated TGF-βreceptor H decreased TGF-β1 autoproduction via blockingTGF-β receptor signaling.