p21活化激酶4在胃癌中的表达及意义

目的探讨p21活化激酶4（PAK4）在人胃癌组织和胃癌细胞系中的表达及与临床病理因素的关系。方法免疫组化法检测95例人胃癌组织中PAK4蛋白的表达；Westernblot法检测40例新鲜胃癌组织和相应的癌旁正常胃黏膜组织以及7种人胃癌细胞系中PAK4蛋白的表达。结果95例人胃癌组织中，PAK4蛋白的阳性表达率为67．4％（64／95），其中62例（96．9％）阳性染色位于细胞浆中，仅有2例（3．1％）位于细胞膜上。PAK4蛋白的阳性表达率与胃癌TNM分期（Χ^2=10．426，P〈0．01）和淋巴结转移（Χ^2=4．912，P〈0．05）有关。新鲜胃癌组织中PAK4蛋白的表达量显著高于癌旁正常胃黏膜组织（t=-5．978，P〈0．01），且随胃癌TNM分期的进展，其表达量逐渐增加。7种人胃癌细胞系中均有PAK4蛋白的表达，与GES-1细胞系相比，PAK4蛋自在ACTS、BGC823、MKN45和N87细胞系中呈高表达，而在MGC803、MKN1和SGC7901细胞系中呈低表达。结论PAK4蛋白的过度表达可能与人胃癌的发生发展及预后有关。     

p21活化激酶4与肿瘤的研究进展

p21活化激酶4(PAK4)是最近发现的一种丝氨酸/苏氨酸蛋白激酶,在一系列细胞功能中发挥重要作用,如细胞周期、细胞增殖、细胞凋亡及细胞骨架重组等.近年研究发现,PAK4在许多肿瘤细胞中过表达,并通过多条信号通路参与肿瘤的发生及迁移浸润.     

p21活化激酶4在恶性肿瘤进展中的生物学作用及其研究进展

p21活化激酶4(PAK4)属于丝氨酸/苏氨酸蛋白家族的一员,在进化上高度保守,通过参与体内多条信号转导通路,影响肿瘤细胞的存活、增殖、侵袭、转移及凋亡等过程,对肿瘤的发生发展有着重要的作用.恶性肿瘤严重威胁人类的生命健康,近年来,随着对恶性肿瘤的深入研究,发现PAK4在肿瘤进展过程中承担着重要的生物学作用.本文就PA...     

p21活化激酶1在胰腺癌中的表达及其意义

 目的　探讨p21活化激酶1（PAK1）蛋白在胰腺癌中的表达及其意义。方法　选取胰腺癌组织标本33例作为研究组,胰腺癌周围正常组织标本33例作为对照组,应用免疫组织化学技术检测组织中PAK1蛋白的表达情况。结果　研究组中PAK1蛋白的阳性表达率明显高于对照组[69.7 %（23／33）比27.3 % （9／33）,χ2＝11.89,P＝0.001];且Ⅲ+Ⅳ期胰腺癌组织中PAK1阳性表达率高于Ⅰ+Ⅱ期[93.3 %（14／15）比50.0 %（9／18）, χ2＝5.367,P＝0.021]。结论　PAK1蛋白可能与胰腺癌发生、发展有关。     

p21激活激酶在肿瘤中的作用及其靶向治疗

p21激活激酶(p21-activated kinases,Paks)是一类丝氨酸/苏氨酸激酶,在进化上高度保守.Paks可被多种上游信号特别是小G蛋白Rho家族的Rac和Cdc42激活,对多种重要的信号通路及细胞功能进行调控.Paks在多种肿瘤中异常表达,参与细胞骨架重构、细胞运动、细胞增殖、分化、凋亡、有丝分裂及血管生成等,在肿瘤的发生、发展中起重要作用.因此,开展Paks靶向治疗的研究,可为肿瘤治疗提供新的思路.     

p21^WAF1／CIP1在乳腺癌中的表达及意义

目的 探讨ｐ２１＾ＷＡＦ／ＣＩＰ１蛋白在乳腺癌中表达的临床意义。方法 动用免疫组化ＳＰ法半定量检测ｐ２１蛋白在癌旁正常乳腺组织、乳腺癌组织中的表达。结果 ｐ２１蛋白表达位于细胞核,呈棕黄色,在２０例癌旁正常乳腺组织中,无ｐ２１蛋白表达。在６９例乳腺癌组织中有３０例ｐ２１蛋白阳性表达。在乳腺癌组织中,随组织学分级升高,ｐ２１阳性率下降（Ｐ〈０．０５）。随临床分期升高,ｐ２１阳性率下降（Ｐ〈０．０５）。有淋巴结转移组ｐ２１阳性率低于无淋巴结转移组（Ｐ〈０．０５）。ｐ２１蛋白阳性表达者术后５年无瘤生存期高于ｐ２１蛋白阴性者术后５年无瘤生存率（Ｐ〈０．０５）。结论 ｐ２１蛋白可用于评估乳腺癌细胞分化情况及转移潜能,可判断乳腺癌患者预后。     

p53和p21在骨巨细胞瘤中的表达及临床意义

目的：探讨p53和p21在骨巨细胞瘤（GCT）的表达及与GCT病理分级和复发的关系。方法：应用SP免疫组织化学方法检测p53,p21在52例GCT中的表达。结果：52例样本中,P53和P21的是性表达率分别为26．9％（14／52）和13．5％（7／52）,两者与病理分级无关（P值分别为0．6999,0．658）,在复发病例中,P53和P21的阳性率分别为46．2％和20．5％,在无复发病例中两者分别为23．1％和10．3％,两者同时表达阳性的有2例,p53和p21同时过表达与GCT复发有显著相关性（P=0\042),结论：p53和p21在GCT中的表达与病理分级无关,与复发相关。     

p16基因在乳腺癌中的表达及临床意义

目的：研究p16基因在乳腺癌中的表达及临床意义。方法：应用免疫组织化学方法（SABC法），检测了92例乳腺癌组织p16基因蛋白的表达。结果：发现p16基因表达阳性率为45．7％（42／92），p16基因表达与腋淋巴结转移无关，但p16阳性者远隔转移率14．3％（6／42）低于p16阴性组34％（17／50，P＜0．05）。本组p16基因表达与疾病缓解期无关。结论：提示p16基因在乳腺癌病程中起重要作用，对筛选乳腺癌术后高危转移患者，加强随访诊治有一定参考意义。     

乳腺癌p21（WAF1）蛋白的表达及临床病理意义

目的：研究p21(WAF1)蛋白在乳腺癌的表达及临床病理意义。方法：应用微波复免疫组化技术S－P法检测了82例乳腺癌及20例乳腺良性病变中p21(WAF1)蛋白的表达,结果： 21(WAF1）蛋白表达位于细胞核中,部分伴有浆染色;p21(WAF1)蛋白在乳腺良性病变细胞核基本不表达,部分有细胞浆着色,乳腺癌中表达率为58．54％（48／82）,其阳性表达与组织高分化,ER阳性,临床分期早有关,与淋巴结有否转移,C－erbB-2,nm23蛋白表达以及是否复发及生存期长短无关。结论：细胞周期调控因子p21(WAF1)蛋白阳性诱导细胞高分化,其缺失在乳腺癌发生发展过程起重要作用。     

乳腺癌中p53,p21蛋白表达和PCNA免疫组化研究及意义

乳腺癌中ｐ５３、ｐ２１蛋白表达和ＰＣＮＡ免疫组化研究及意义王淑真庄严阵张海萍江显毅陈琦杨萌霓陈佩琼方庆全厦门市第一医院病理科（厦门市３６１００３）１材料与方法本组４７例取自我院１９９５～１９９６年间乳腺癌根治术标本，取癌组织、癌旁组织及正常组织，石...     

p21-activated kinase 1: PAK'ed with potential

The p21-activated kinases (PAKs) are central players in growth factor signaling networks and morphogenetic processes that control proliferation, cell polarity, invasion and actin cytoskeleton organization. This raises the possibility that interfering with PAK activity may produce significant anti-tumor activity. In this perspective, we summarize recent data concerning the contribution of the PAK family member, PAK1, in growth factor signaling and tumorigenesis. We further discuss mechanisms by which inhibition of PAK1 can arrest tumor growth and promote cell apoptosis, and the types of cancers in which PAK1 inhibition may hold promise.     

Discovery and the structural basis of a novel p21-activated kinase 4 inhibitor

Functional versatility and elevated expression in cancers have endowed p21-activated kinase 4 (PAK4) as one of the first-in-class anti-cancer drug target. In this study, a novel PAK4 inhibitor, KY-04031 (N²-(2-(1H-indol-3-yl)ethyl)-N⁴-(1H-indazol-5-yl)-6-methoxy-1,3,5-triazine-2,4-diamine), was discovered using a high-throughput screening. Analysis of the complex crystal structure illustrated that both indole and indazole of KY-04031 are responsible for PAK4 hinge interaction. Moreover, the molecule’s triazine core was found to mimic the ribose of the natural ATP substrate. The cell-based anti-cancer potency of KY-04031 was less effective than the pyrroloaminopyrazoles; however, the unique molecular feature of KY-04031 can be exploited in designing new PAK4 inhibitors.     

不同人乳腺肿瘤细胞系中Jagged1基因和蛋白的表达水平

目的:研究Jagged1蛋白和mRNA在人乳腺癌细胞系中的表达。方法:分别使用蛋白印迹法及实时定量聚合酶链式反应检测Jagged1蛋白和基因在人乳腺癌细胞系中的表达情况。结果:Jagged1在不同的人乳腺肿瘤细胞系中蛋白和基因的表达水平不同。结论:Jagged1蛋白在人乳腺癌细胞系ZR-75-30和MDA-MB-231中高表达,Jagged1基因在人乳腺癌细胞系MDA-MB-231,HCC 1937中高表达,Jagged1可能是在人乳腺癌的发展进程中发挥着重要的作用。     

p21-activated kinase signaling in breast cancer

The p21-activated kinases signal through a number of cellular pathways fundamental to growth, differentiation and apoptosis. A wealth of information has accumulated at an impressive pace in the recent past, both with regard to previously identified targets for p21-activated kinases that regulate the actin cytoskeleton and cellular stress pathways and with regard to newly identified targets and their role in cancer. Emerging data also provide new clues towards a previously unappreciated link between these various cellular processes. The present review attempts to provide a quick tutorial to the reader about the evolving significance of p21-activated kinases and small GTPases in breast cancer, using information from mouse models, tissue culture studies, and human materials.     

p21-activated kinase signaling in breast cancer

The p21-activated kinases signal through a number of cellular pathways fundamental to growth, differentiation and apoptosis. A wealth of information has accumulated at an impressive pace in the recent past, both with regard to previously identified targets for p21-activated kinases that regulate the actin cytoskeleton and cellular stress pathways and with regard to newly identified targets and their role in cancer. Emerging data also provide new clues towards a previously unappreciated link between these various cellular processes. The present review attempts to provide a quick tutorial to the reader about the evolving significance of p21-activated kinases and small GTPases in breast cancer, using information from mouse models, tissue culture studies, and human materials.     

Overexpression of P21-activated kinase 4 is associated with poor prognosis in non-small cell lung cancer and promotes migration and invasion

Background

P21-activated kinase 4 (PAK4), an effector of the Rho family protein Cdc42, is an important oncogene whose expression is increased in many human cancers and is generally positively correlated with advanced disease and decreased survival. However, little is known about the expression and biological function of PAK4 in human non-small cell lung cancer (NSCLC).

Methods

PAK4 expression in NSCLC tissues and adjacent non-tumor tissues were assessed by immunohistochemistry, real-time PCR, and western blotting. Prognostic value of PAK4 expression was evaluated by Kaplan-Meier analysis and Cox regression. siRNA-mediated gene silencing and protein kinase assay was applied to demonstrate the role and the mechanism of PAK4 in lung cancer cell migration, invasion.

Results

The results showed that PAK4 was overexpressed in NSCLC cell lines and human NSCLC tissues. PAK4 expression was detected both in the membranes and cytoplasm of NSCLC cancer cells in vivo. Moreover, increased expression of PAK4 was associated with metastasis, shorter overall survival, advanced stage of NSCLC. Furthermore, PAK4 expression was positively correlated with phosphorylation of LIMK1 expression levels. Knockdown of PAK4 in NSCLC cell lines led to reduce the phosphorylation of LIMK1, which resulted in decrease of the cell migration and invasion. In addition, PAK4 bound to LIMK1 directly and activated it via phosphorylation.

Conclusions

These data demonstrate that PAK4 mediated LIMK1 phosphorylation regulates the migration and invasion in NSCLC. Therefore, PAK4 might be a significant prognostic marker and potential therapeutic molecular target in NSCLC.     

泛素特异性肽酶22在胃癌细胞系中的表达和定位

目的:研究泛素特异性肽酶22(USP22)蛋白和信使核糖核酸(mRNA)在人胃癌细胞中的表达和定位.方法:分别用蛋白印迹法、实时荧光定量聚合酶链反应检测USP22在人胃癌细胞系中蛋白和基因的表达,激光共聚焦扫描显微镜检测内源USP22在SGC7901胃癌细胞中的定位.结果:USP22在人胃癌细胞系SGC7901中蛋白和基因表达水平增高,激光共聚焦扫描显微镜观察发现USP22主要定位于SGC7901细胞核中.结论:USP22在人胃癌细胞系SGC7901中高表达,主要定位于胃癌细胞核内,可能参与人胃癌发生发展的进程.     

p21-激活激酶1在大肠癌组织中的表达及其临床意义

 目的　探讨p21-激活激酶1（PAK1）基因在大肠癌组织中的表达及其临床病理学意义。方法　采用免疫组织化学SABC法检测50例大肠癌组织及癌旁正常组织PAK1基因的表达,并分析其与各临床病理参数之间的关系。结果　癌组织中PAK1蛋白表达阳性率显著高于癌旁正常组织（58 %∶22 %）,差异有统计学意义（P＜0.01）,定位于癌细胞胞质,并与淋巴结转移、组织分化程度密切相关（χ2＝8.872,P＝0.003;χ2＝6.344,P＝0.042）,与肿瘤部位、大小、患者的性别和年龄无关（P＞0.05）。结论　PAK1过度表达同大肠癌的生物学行为密切相关,在大肠癌的发生、发展过程中具有重要的作用。