前列腺癌及其癌前病变中抑癌基因p16的表达

ｐ１６基因（ＭＴＳ１）是新近发现的一种抑癌基因,其突变广泛而高频率地存在于各种人肿瘤细胞。ｐ１６基因可能与肿瘤的发生发展有关。我们应用抑癌基因ｐ１６的多克隆抗体,采用微波免疫组织化学方法,观察了抑癌基因ｐ１６在前列腺癌及其癌前病变中的表达情况,探讨ｐ...     

p33ING1基因及其研究进展

抑癌基因对于肿瘤的发生具有抑制作用 ,细胞内一种或多种抑癌基因的失活可以导致肿瘤的发生。迄今 ,在为数不多的抑癌基因中 ,与肿瘤关系最密切、研究最为广泛的可能是ｐ5 3基因。近年来又发现了一种与ｐ5 3密切相关的新基因ｐ3 3ＩＮＧ1,它对ｐ5 3功能的发挥可能起至关重要的作用。一、ｐ3 3ＩＮＧ1的发现1996年 ,Ｇａｒｋａｖｔｓｅｖ等[1] 在减数杂交的基础上 ,用一种ｇｅｎｅｔｉｃｓｕｐｐｒｅｓｓｏｒｅｌｅｍｅｎｔ(ＧＳＥ)方法 ,克隆出一个新基因。用该基因ｃＤＮＡ片段反向插入表达载体并转染小鼠永生化乳腺上皮细胞后 ,接种于裸鼠…     

p73—一个p53家族新基因

ｐ７３基因是一新发现的与经典抑癌基因ｐ５３具有相似结构,功能和活性的基因,并由于其在染色体上特殊的定位,被认为是一种新的候选抑癌基因。本介绍了ｐ７３发现以来国外有关ｐ７３基因的研究进展,特别对ｐ７３基因的定位、ｐ７３与ｐ５３的关系、是否抑癌基因以及该基因在肿瘤发生发展中的作用和地位进行了综述。     

P53基因在鼻咽癌治疗中的研究进展

转录因子P53作为一种抑癌基因,可诱导细胞生长阻滞,细胞凋亡,细胞分化以及DNA修复。但P53突变体可能会使野生型P53基因的抑癌功能失活,甚至发挥癌基因的功能。随着分子生物技术的发展,人们对P53基因结构及功能、与肿瘤发生的关系、肿瘤治疗尤其在鼻咽癌应用方面有很多新认识,因此就P53基因结构及功能、与肿瘤发生的关系、肿瘤治疗及在鼻咽癌应用方面的新进展进行综述。     

抑癌基因p21

抑癌基因Ｗａｆｌ／Ｃｉｐｌ／ｐ２１（Ｗｉｌｄ┐ｔｙｐｅ┐ｐ５３┐ａｃｔｉｖａｔｅｄｆｒａｇｍｅｎｔ／ＣＤＫ┐ｉｎｔｅｒａｃｔｉｎｇｐｒｏｔｅｉｎ１／ｐ２１）既与肿瘤抑制作用密切相关，又能通过抑制周期素┐周期素依赖激酶（Ｃｙｃｌｉｎ┐ＣＤＫｓ）复合物活性，协调细胞周期、ＤＮＡ复制与修复之间的关系，从而将肿瘤抑制作用与细胞周期控制过程紧密相连。ｐ２１基因的发现、克隆及其在细胞周期控制与肿瘤发生中有重要作用     

LSAB法在检测恶性肿瘤抑癌基因p53蛋白表达中的应用与体会

ＬＳＡＢ法在检测恶性肿瘤抑癌基因ｐ５３蛋白表达中的应用与体会牛兆山ｐ５３基因是一种重要的抑癌基因，ｐ５３蛋白的异常表达与恶性肿瘤的发生、发展有关。随着对检测ｐ５３蛋白技术手段的不断研究，方法将日趋完善。目前常见的检测法有ＲＦＬＰ、ＰＣＲ及免疫组化技术...     

抑癌基因p16研究进展

ｐ１６作为一个不同于ｐ５３的新发现的抑癌基因，为细胞周期与肿瘤发生机制的研究提供了新的途径，对今后肿瘤的治疗将具重要意义。对ｐ１６基因结构、定位、突变、表达情况以及作用机制作一综述     

p73-一个p53家族新基因

p73基因是一新发现的与经典抑癌基因p5 3具有相似结构、功能和活性的基因 ,并由于其在染色体上特殊的定位 ,被认为是一种新的候选抑癌基因。本文介绍了p73发现以来国外有关p73基因的研究进展 ,特别对p73基因的定位、p73与p5 3的关系、是否抑癌基因以及该基因在肿瘤发生发展中的作用和地位进行了综述。     

脆性组氨酸三联体(FHIT)基因

人类第3号染色体上的基因座在不同的肿瘤组织中出现高频率的杂合性丢失(LOH),提示该部位可能是抑癌基因潜伏的位点。最近克隆的脆性组氨酸三联体基因(fragile histidine triad,FHIT)可能是定位于染色体3p14.2的一个抑癌基因,该基因在肿瘤组织中广泛地缺失为研究肿瘤发生机制提供了新线索。     

骨肉瘤癌基因与抑癌基因研究进展

现代分子遗传学证实：骨肉瘤的发生和演进是以癌基因激活和／或抑癌基因失活为主的多基因异常累加的结果。业已证实：Ｒｂ、ｐ５３－ｃ－ｍｙｃ、ｆｏｓ和ｃ－ｅｒｂＢ２等在骨肉瘤发生中较常出现异常改变。最近研究发现骨肉瘤中ＤＣＣ、ｐ１６和ｐ１５抑癌基因出现异常；证实３号染色体长臂（３ｑ）上存在骨肉瘤抑癌基因并将其定位在３ｑ２６和Ｄ３Ｓ１２１２和Ｄ３Ｓ１２４６之间；对ＭＤＭ２和ＳＡＳ癌基因、Ｒｂ和ｐ５３抑癌基因     

p73：人类非小细胞肺癌细胞株中的肿瘤抑制基因(英文)

目的：p73基因是与p53相类似的基因,在人类神经母细胞瘤中被假定作为肿瘤抑制基因。为了证实p73在非小细胞肺癌中是否也是肿瘤抑制基因，我们应用StyⅠ内切酶多态分析法研究了6株非小细胞肺癌细胞的等位基因表达模式。方法：利用RT-PCR检测p73基因在这6株肺癌细胞中转录水平的表达，同时用免疫组织化学方法检测5株非小细胞肺癌细胞所诱发的裸鼠种植瘤中P73蛋白的表达。结果：p73基因在这6株非小细胞肺癌中均为纯合性等位基因表达，而GC/GC基因型为主要类型。p73基因在转录水平和蛋白水平完全丧失表达。结论：根据实验结果可推测，p73在这6株非小细胞肺癌细胞中仍扮演了肿瘤抑制基因的角色。     

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。     

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.     

心血管系统中PTEN基因的研究进展

<正>PTEN基因于1997年由3个研究小组先后克隆并命名,是迄今发现的第一个具有双特异磷酸酶活性的抑癌基因,其在细胞生长、凋亡、细胞周期阻滞、细胞迁移过程起关键作用,成为新近研究的热点。     

TP53 family members and human cancers

Based on gene sequence homologies, a p53 (TP53) gene family become apparent with the addition of the most recently identified p63 (TP73L; formerly TP63) and p73 (TP73) genes to the already known p53. The p53 gene encodes for a unique protein eliciting well-known tumor suppressor gene (TSG) properties that mediate cellular response to DNA damage, e.g., cell cycle arrest or apoptosis. In contrast, both homologues specify an array of isoforms different in their N- and C-terminal domains. Transactivating isoforms, such as TAp63/p73, show TSG properties similar to p53, while isoforms lacking N-terminal transactivating domain such as DeltaNp63/p73, induce a functional block against p53 as well as TAp63/p73 activities. Both p63/p73 types of isoforms are involved in development: p63 is critical for epithelial stem cell renewal and epithelial homeostasis, and p73 is involved in neurogenesis and natural immune response. These facts support interdependent functions for the p53 family members, which appear linked together in a complex and tight regulation network to fulfill cellular functions related to DNA damage and tissue homeostasis maintenance. The lack of p63/p73 mutations in human cancers rule out a typical TSG role for either of the p53 homologues. Nonetheless, p63 and p73 genes seem strongly involved in malignancy acquisition and maintenance process because of: 1) their tissue identities, and 2) their close interplay activities within the p53 family members, and primarily through the negative regulatory role played by DeltaNp63/p73 isoforms for cell death control and differentiation.     

Differential expression of p53 gene family members p63 and p73 in head and neck squamous tumorigenesis

p73 and p63 are recently cloned genes that share considerable structural and functional homologies with the p53 tumor suppressor gene. These genes, unlike p53, express multiple mRNA isoforms with variable biologic functions, and their suppressor nature has yet to be confirmed. To determine the interrelationship between these genes in the tumorigenesis of head and neck squamous carcinoma (HNSC), we performed immunohistochemical analyses of their protein products and compared the data with clinicopathologic parameters in 38 patients. In histologically normal epithelium, p53 and p73 showed similar basal and/or parabasal expression, but that of p53 was weaker and discontinuous. p63 staining was noted in more suprabasal cellular layers and was stronger. In dysplasias, all three markers manifested variable but gradual increase in extent and intensity of cellular expression with histologic progression. In carcinomas, p63 was the most frequently expressed (94.7%), followed by p73 (68.4%) and p53 (52.6%). Significant statistical correlation was noted only between p63 and p73 expressions (P =.04). Although no statistical correlation was found between p53 and p63 or p73, p53-negative tumors overexpressed either p63 or p73. p73 expression was associated with distant metastasis and perineural/vascular invasion. Our study indicates that (1) p63 and p73 expression may represent an early event in HNSC tumorigenesis, (2) the lack of correlation between p73 or p63 and p53 expression suggests an independent and/or compensatory functional role, (3) p73 expression may play a part in HNSC progression, and (4) p73 and p63 may function as oncogenes in the development of these tumors.     

The jury is in: p73 is a tumor suppressor after all

While p53 has been extensively characterized as a tumor suppressor, it has been more difficult to determine whether p63 and/or p73 play a similar role. Every system in which these family members have been studied, from cells to animal models to human tissues, seems to create more questions than answers. Tomasini and colleagues (2677-2691) demonstrate that one isoform of p73 is responsible for preventing tumor formation in vivo, providing critical validation of an isoform-based model of p73 function.     

鼻咽癌,宫颈癌和肺癌中p53基因突变和表达的对比研究

目的对比研究ｐ５３在鼻咽癌、宫颈癌、肺癌中的表达及其与ｐ５３基因突变的关系，为进一步研究ｐ５３在癌变过程中的作用奠定基础。方法应用免疫组化结合ＰＣＲ－ＳＳＣＰ银染技术检测２４例鼻咽癌、９例宫颈癌、１０例肺癌中ｐ５３基因的表达与突变。结果２３／２４例鼻咽癌、６／９例宫颈癌、９／１０例肺癌有ｐ５３的过表达，在两种发病与ＤＮＡ致瘤病毒有关的鼻咽癌、宫颈癌中未能检测到ｐ５３基因突变；而发病与化学致癌物有关的肺癌中有５／１０例检测到有ｐ５３基因突变，其中１例发生在外显子８，４例发生在外显子５。这５例均有ｐ５３的过表达。结论（１）鼻咽癌、宫颈癌、肺癌中存在着ｐ５３蛋白的过表达。（２）肺癌中ｐ５３的过表达大部分与ｐ５３基因突变有关，而鼻咽癌与宫颈癌中ｐ５３过表达与ｐ５３基因突变关系不大，其与致瘤性ＤＮＡ病毒的作用是否有关有待进一步研究。     

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.     

p53对肝癌细胞株Hep3BP-糖蛋白表达和耐药表型的影响

目的:验证野生型p53调节肝癌细胞P-糖蛋白(P-gp)表达的设想。方法:通过采用脂质体介导转染技术,将野生型p53cDNA导入一种p53和Rb基因缺失的肝癌细胞株Hep3B。经G418筛选获得稳定整合了野生型p53的克隆(wt-p53)和空载体克隆(pNeo)。采用Northern或Western印迹鉴定p53、p21和P-gp的表达;细胞毒性试验分析细胞对化疗药的敏感性;流式细胞仪检测细胞内阿霉素的积累浓度。结果:wt-p53细胞表达有转录活性的p53,p21^waf1/cip1蛋白升高,P-gp表达降低,与pNeo细胞相比对阿霉素和丝裂霉素化疗敏感且阿霉素荧光量为pNeo细胞的13倍。采用0.2mg/L阿霉素诱导这2组转染细胞,wt-p53细胞出现明显的凋亡。结论:在肝癌细胞Hep3B中重建野生型p53的活性由于降低P-gp的表达而对化疗药敏感。