p53、p63及p73在皮肤血管瘤组织中的表达

目的　为探讨p5 3p6 3及p73蛋白在皮肤血管瘤组织中的表达及意义。方法　采用免疫组织化学S P法和图像分析技术检测 4 0例血管瘤组织和 2 0例正常皮肤组织中p5 3、p6 3及p73基因的表达。结果　在增生期血管瘤、退化期血管瘤和正常皮肤组之间 ,p73蛋白免疫组化阳性反应颗粒的平均光密度分别为 6 4 0 8± 2 15 1、1 0 73± 0 5 16和 0 95 3± 0 12 0。p6 3蛋白免疫组化阳性反应颗粒的平均光密度分别为 8 2 71± 1 95 3、0 92 3± 0 191和 0 92 0± 0 187。p5 3蛋白免疫组化阳性反应颗粒的平均光密度分别为 7 2 4 0± 1 874、0 934± 0 187和 0 92 3± 0 16 5。增生期血管瘤与退化期血管瘤、正常皮肤组分别组比 ,p73、p6 3及p5 3阳性表达的差异均有高度显著性差异 (P <0 0 0 1) ,消退期血管瘤与正常皮肤组之间 ,p73、p6 3及p5 3阳性表达差异无显著性 (P >0 0 5 )。结论　在增生期血管瘤组织中p73、p6 3及p5 3呈高表达 ,促进了内皮细胞的增殖 ,是导致血管瘤发生、发展的主要因素     

p73: structure and function

Alteration of the p53 tumor suppressor gene is a common, if not general, observation in human malignant tumors. p73 Is a novel member of the p53 family at chromosome 1p36.3, at which locus frequent defects are seen in many tumors including neuroblastoma. Besides structural similarities, the fact that p73 functions in the regulation of the cell cycle and apoptosis promotes the expansion of the research field concerning p53-associated tumor progression. In this paper, we review the structure and function of p73 as well as the mutational status in various human tumors. In addition, possibilities for new therapeutic applications with p73 for cancer cell control are discussed.     

p73基因研究进展

p73是最近发现的p53家族的一员,它与p53不仅在蛋白结构上具有较高的同源性,功能也具有一定的相似性,被认为是一种潜在的抑癌基因。但随着研究的深入,发现P73在功能和调控机制上与P53都具有不同点。P73具有诱导细胞凋亡的能力,其机制与P53不同。P73在很多肿瘤中的表达高于相应的正常组织,这与经典的抑癌基因也不同。因此对于P73基因仍需进一步的研究。     

阿糖胞苷诱导肺腺癌细胞凋亡与p73激活相关

目的 体外观察阿糖胞苷(1-β-D-arabinofuranosylcytosine, Ara-C)对肺腺癌A549细胞凋亡的诱导作用,探讨p53、p73基因在此凋亡过程中的调控作用.方法 Ara-C体外作用于A549细胞,TUNEL法检测A549细胞的凋亡;透射电镜观察A549细胞凋亡的典型超微结构;免疫印迹法检测A...     

卵巢癌中野生型p73基因的表达水平的研究

目的　研究p73基因在卵巢癌与癌旁正常组织中表达水平及其意义。方法　采用竞争性定量RT -PCR方法检测 38例卵巢癌及其癌旁正常组织中p73基因表达水平。结果　通过定量RT -PCR分析 ,发现卵巢癌组织中p73基因的表达水平比正常对照组织中平均高出 5倍 ,表达量存在显著差异 (P <0 0 1)。结论　p73基因的高表达与卵巢癌的发生发展有密切关系。     

甲状腺癌中p73蛋白的表达

目的：探讨p73蛋白在甲状腺癌中的表达及其临床意义。方法：选取甲状腺癌病理石蜡标本107例和良性甲状腺病变组织31例,采用免疫组化S-P法检测p73基因在甲状腺癌和良性甲状腺病变组织中的表达情况。结果：107例甲状腺癌组织中p73阳性率为66.4%,与良性甲状腺病变组织有显著性差异（P〈0.05）。结论：p73基因的表达可能与甲状腺癌的发生、发展有关。     

食管癌中p73蛋白的表达及与临床病理特征的关系

目的:检测p73蛋白在食管癌组织中的表达情况,并探讨其与食管癌临床病理特征的关系。方法:采用免疫组化检测p73蛋白在53例食管磷癌及癌旁组织中的表达情况。结果:p73蛋白在食管癌组织中的阳性表达率为84.9%(45/53),而在癌旁食管粘膜组织中的阳性表达率为32.7%(17/53),两者比较有显著性差异(P<0.01)。p73蛋白的表达与食管磷癌分化程度密切相关(P<0.05),其在低分化癌组织中的阳性表达率(94.7%)显著高于在高分化癌组织中的阳性表达率(61.5%)。p73蛋白的表达与食管磷癌的TNM分期、淋巴结转移、浸润深度均无明显相关性(P>0.05)。结论:p73蛋白在食管磷癌组织中呈高表达,表明可能参与食管癌的发生。     

A mechanism of ubiquitin-independent proteasomal degradation of the tumor suppressors p53 and p73

Protein degradation is an essential and highly regulated process. The proteasomal degradation of the tumor suppressors p53 and p73 is regulated by both polyubiquitination and by an ubiquitin-independent process. Here, we show that this ubiquitin-independent process is mediated by the 20S proteasomes and is regulated by NQO1. NQO1 physically interacts with p53 and p73 in an NADH-dependent manner and protects them from 20S proteasomal degradation. Remarkably, the vast majority of NQO1 in cells is found in physical association with the 20S proteasomes, suggesting that NQO1 functions as a gatekeeper of the 20S proteasomes. We further show that this pathway plays a role in p53 accumulation in response to ionizing radiation. Our findings provide the first evidence for in vivo degradation of p53 and p73 by the 20S proteasomes and its regulation by NQO1 and NADH level.     

乳腺增生性病变中p63蛋白的表达及意义

目的 探讨p63蛋白在乳腺疾病诊断以及鉴别诊断中的应用价值。方法 对38例不同类型的乳腺病变分别进行p63、SMA、S-100蛋白、CK(34βE12)免疫标记。结果 p63蛋白在乳腺良性增生性病变腺体肌上皮细胞核有阳性表达,围绕在腺体周围,原位癌癌巢周围肌上皮细胞数目减少,呈间断性分布,浸润性癌癌巢周围肌上皮细胞大部分消失或无肌上皮细胞分布,且阳性表达强度与肿瘤分化程度相关。其他基底细胞标记物也可以比较特异地显示乳腺腺体周围肌上皮,但存在一定的非特异性着色。结论 从乳腺正常组织、良性病变至原位癌、早期浸润和浸润性癌,腺体周围的肌上皮细胞呈逐渐消失的趋势,p63蛋白标记可以比较特异地反映这个过程,而且受其他影响因素小。     

Regulating p73 isoforms in human tumours

Although mutations in the TP73 gene are extremely rare in human tumours, altered expression is common. In some tumours, most notably leukaemias and lymphomas, expression of TP73 is reduced, suggesting a tumour suppressor role. In contrast, TP73 is over-expressed in many other tumour types, implying that it has oncogenic functions in human tumourigenesis. These conflicting scenarios can be reconciled by the observations that the TP73 gene produces p53-like isoforms (TAp73) and anti-p53 isoforms (DeltaTAp73). Thus, loss of TAp73 or over-expression of DeltaTAp73 should each promote oncogenic transformation, and the balance of expression of the opposing isoforms is the crucial factor. The mechanisms that regulate expression of TP73 isoforms are therefore of great interest. Recent data provide evidence for interacting roles of ZEB1, p300, and a polymorphic 73 bp deletion in intron 1 of the human TP73 gene in this process. Importantly, alterations to the proposed regulatory pathway for controlling TP73 isoform expression in colorectal cancer are associated with adverse clinico-pathological characteristics. Because p73 is also associated with tumour chemosensitivity, these new findings should provide prognostic information and have the potential to guide future therapeutic decisions.     

Aberrant p53 protein expression in cervical intra-epithelial neoplasia

We investigated aberrant p 53 expression in 81 cases of cervical intra-epithelial neoplasias (CIN) using a polyclonal antibody CM-1. The presence of human papillomavirus (HPV) DNA was evaluated by in situ and dot blot hybridization. Significant (more than 1% of cells positive) p 53 positivity was found in three cases (4%) of which only one contained HPV DNA. In an additional nine cases, occasional p 53 staining was found in basal epithelial cells, frequently associated with epithelial hyperplasia and increased subepithelial inflammation. The results show that aberrant p 53 expression is an infrequent finding in CIN lesions. It can be seen in lesions both with and without HPV infection. Most importantly, there was no p 53 expression in most cases of HPV-negative CIN, suggesting that p 53 inactivation is not an obligatory step in the development of cervical dysplasia. However, our findings do not exclude the possibility that p 53 mutations can occur later in the course of cervical carcinogenesis.     

口腔鳞癌及癌前病变组织中p27、p53蛋白的表达

目的　探讨 p2 7、p5 3蛋白表达在口腔鳞癌发生发展中的意义。 方法　应用免疫组化S P法分别检测 9例口腔正常黏膜 ,11例单纯性增生、2 6例癌前病变及 5 4例鳞癌组织中p2 7、p5 3蛋白的表达。 结果　p2 7蛋白在口腔正常黏膜和单纯性增生组织中呈高表达 ,在癌前病变和鳞癌组织中高 (低 )表达率分别为 6 1 5 % (38 5 % )、2 5 9% (6 1 1% ) ,在鳞癌中阴性表达率为 13% ;p2 7蛋白的表达与鳞癌的组织分化程度、临床分期相关 (P <0 0 5 )。p5 3蛋白在正常黏膜、单纯性增生及轻、中度不典型增生中未见表达 ,在重度不典型增生和鳞癌中可见 2 8 6 %和 4 8 1%的阳性表达 ,二者差异有高度显著性 (P <0 0 1) ;在鳞癌中 p5 3蛋白表达与组织分化程度相关 (P <0 0 5 ) ;p2 7和p5 3表达在鳞癌中呈负相关 (P <0 0 1)。 结论　p2 7蛋白表达的减少在口腔鳞癌的发生发展中起着重要作用 ,并与其预后因素密切相关。p5 3蛋白的表达在癌前病变向鳞癌转变过程中起重要作用。综合分析 p2 7、p5 3表达有助于口腔鳞癌的早期诊断和患者预后的估计。     

p73基因在卵巢上皮性肿瘤中的表达及甲基化研究

目的 探讨卵巢上皮性肿瘤中p73蛋白的表达和基因启动子的甲基化情况,并观察其与临床病理学特征的关系.方法 制备包括68例卵巢癌、37例卵巢交界性肿瘤和21例卵巢良性肿瘤的组织芯片,用免疫组织化学EnVision法检测上述组织中p73蛋白表达情况,用亚硫酸氧盐修饰后测序法检测13例新鲜卵巢癌组织及5例新鲜卵巢交界性肿瘤组织的p73基因启动子甲基化情况.结果 92.6％ (63/68)的卵巢癌表达p73,p73蛋白总体表达率均值为32％(p73表达率指p73阳性细胞数所占的百分比),其中浆液性癌( 26/26)的表达率均值为40％,高于其他组织类型的癌(P=0.006).按照卵巢癌发病模式区分,Ⅱ型卵巢癌p73表达率均值(40％)高于Ⅰ型卵巢癌(24％),P=0.010.卵巢癌中p73的表达与临床分期及组织学分级无相关性(均P＞0.05).卵巢交界性肿瘤组(30/37)和良性肿瘤组(12/21)p73的总体表达率均值分别为16％和15％,该两组肿瘤中浆液性肿瘤表达率均值均高于黏液性肿瘤(P-0.003,P=0.026).卵巢癌组的p73阳性表达率均值明显高于交界性肿瘤组和良性肿瘤组(均P ＜0.05),交界性肿瘤组与良性肿瘤组比较差异无统计学意义(P＞0.05).浆液性肿瘤( 49/53)中,卵巢癌组(26/26) p73阳性表达率均值明显高于交界性肿瘤组(12/14)和良性肿瘤组(11/13;P =0.024和P=0.002),而卵巢交界性肿瘤组和良性肿瘤组比较差异无统计学意义(P=0.428).黏液性肿瘤(15/27)中,卵巢癌组(6/7)p73阳性表达率均值高于良性肿瘤组( 1/8;p=0.032),而卵巢癌组与卵巢交界性肿瘤组(8/12)、交界性肿瘤组与良性肿瘤组比较,差异均无统计学意义(P=0.234和P=0.201).p73启动子的甲基化结果显示,13例卵巢癌有8例发生甲基化,但每例样本甲基化频率有所不同,总体甲基化频率均值为8.0％.5例交界性肿瘤有2例发生甲基化,总体甲基化频率均值为9.0％,两组比较差异无统计学意义(P＞0.05).卵巢癌组p73甲基化额率与组织类型、发病模式、组织学分级及临床分期均无相关性(均P＞0.05).结论 卵巢上皮性肿瘤多数表达p73,卵巢癌p73的表达率均值明显高于交界性肿瘤和良性肿瘤,浆液性肿瘤高于其他组织类型;p73蛋白表达率与p73基因甲基化程度不存在简单线性相关关系.     

卵巢肿瘤组织p73蛋白表达的研究

目的研究卵巢上皮性肿瘤组织中p73蛋白的表达,探讨它们在卵巢肿瘤发生发展中的作用。方法应用免疫组化SP法检测p73蛋白在15例良性,12例交界性,50例恶性肿瘤和15例正常卵巢组织中的表达,用Pearsonχ2检验p73基因的表达在四组间是否有差别。结果p73蛋白在良性肿瘤中表达率为26.7%（2/15）;在交界性肿瘤阳性表达率为50%（6/12）;在恶性肿瘤阳性表达率为76%（38/50）;在正常组织表达率为13.3%（1/15）。恶性肿瘤与良性肿瘤,恶性肿瘤和正常组织间差异具有显著性（P〈0.05）;恶性肿瘤和交界性肿瘤间无明显相关性（P〉0.05）。p73蛋白表达与癌肿细胞分型相关：粘液性肿瘤p73以胞核阳性表达为主,浆液性肿瘤p73以胞浆阳性表达为主。结论突变型p73基因的高表达可作为判断卵巢上皮性肿瘤良、恶性的指标之一,p73基因的表达类型与细胞分型有关。     

TAp73 depletion accelerates aging through metabolic dysregulation

Aging is associated with impaired scavenging of reactive oxygen species (ROS). Here, we show that TAp73, a p53 family member, protects against aging by regulating mitochondrial activity and preventing ROS accumulation. TAp73-null mice show more pronounced aging with increased oxidative damage and senescence. TAp73 deletion reduces cellular ATP levels, oxygen consumption, and mitochondrial complex IV activity, with increased ROS production and oxidative stress sensitivity. We show that the mitochondrial complex IV subunit cytochrome C oxidase subunit 4 (Cox4i1) is a direct TAp73 target and that Cox4i1 knockdown phenocopies the cellular senescence of TAp73-null cells. Results indicate that TAp73 affects mitochondrial respiration and ROS homeostasis, thus regulating aging.     

大鼠脑慢性缺血状态再灌注对海马区神经细胞凋亡及p21和p53蛋白表达的影响

目的通过建立大鼠慢性脑缺血再灌注模型,观察再灌注时大鼠海马区神经细胞凋亡及p53和p21蛋白的表达。方法70只健康雄性SD大鼠随机分为对照组(n=10),模型组(n=30),模型再灌注组(n=30),应用TUNEL法检测细胞凋亡情况,用免疫印迹法检测大鼠海马p53和p21蛋白的表达。结果对照组未见凋亡细胞,模型组凋亡细胞数明显少于模型再灌注组(p<0.05);p53和p21蛋白在对照组无表达,模型组表达少于模型再灌注组(p<0.05),术后48h达高峰,72h后逐渐降低。结论慢性脑缺血再灌注后海马神经细胞凋亡,海马区p53和p21蛋白表达上调可能参与正常灌注压突破综合症发病机制。