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野生型p14ARF基因转染对人肺癌细胞生长抑制的这实验研究 总被引:1,自引:0,他引:1
目的 探讨外源性p14ARF基因能否对体内外生长的肺癌细胞起抑制增殖的作用。方法 选择4株具有不同基因背景的肺癌细胞系,转染人的野生型p14ARF基因。通过RT-PCR、免疫组化及Westernblot杂交检测,筛选出同时表达p14ARF mRNA及蛋白的阳性克隆。以母细胞及转染空载体细胞为对照,比较它们的增殖、细胞周期分布、裸鼠体内成瘤性以及形态学上的差异。结果 三株具有野生型p53基因的肺癌细胞在转染p14ARF基因后,细胞周期被显著阻滞于G1或G1/G2期,增殖受到抑制。结论 外源性野生型p14ARF基因转染能抑制人肺癌细胞的增殖,p14ARF基因是人体肺癌基因治疗的理想侯选基因。 相似文献
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p14ARF、p53蛋白表达与H101治疗鼻咽癌疗效的关系 总被引:2,自引:0,他引:2
目的:观察肿瘤组织p14^ARF、突变型p53蛋白表达状态与E1B缺陷型腺病毒治疗鼻咽癌疗效的关系,探讨E1B缺陷型腺病毒(简称H101)基因治疗的作用机制。方法:应用免疫组织化学方法对36例H101治疗的晚期鼻咽鳞癌病例进行肿瘤组织p14^ARF、突变型p53蛋白检测,分析肿瘤组织p14^ARF、突变型p53蛋白表达与H101临床疗效的关系;结果:突变型p53和p14^ARF蛋白在36例晚期鼻咽鳞癌中总阳性表达率分别为55.6%和44.4%;突变型p53^+p14^ARF(即p14^ARF蛋白无缺失)患者均无治疗有效病例;突变型p53^+p14^ARF-(即p14^ARF蛋白有缺失)患者中有4例有效;结论:对于p53基因无突变的恶性肿瘤,p14ARF基因缺失可能是H101能在肿瘤细胞内有效复制并杀死肿瘤细胞的一个重要影响因素。 相似文献
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目的 研究POKemon、p14ARF基因在结直肠癌细胞系中的表达情况.方法 采用反转录.聚合酶链反应(RT-PCR)、细胞免疫化学技术检测POKemon、p14ARF在5种人类结直肠癌细胞中的表达.结果 POKemon在SW480、SW480/M5、LOVO、SW620中阳性表达,在HCT116阴性表达;p14ARF在HCT116阳性表达,其余细胞均阴性表达.结论 结直肠癌细胞系中存在POKemon的表达,且与p14ARF作用呈负相关.Abstract: Objective To study the expression of POKemon and pl4ARF genes in colorectal cancer cell lines. Methods The expressions of POKemon and pl4ARF were detected in 5 human colorectal cancer cell lines by RT-PCR and immucytochemistry method. Results The expressions of POKemon were positive in cell lines of SW480, SW480/M5, SW620 and LOVO, and were negative in HCT116. The expression of pl4ARF was positive in HCT116 and negative in other cell lines. Conclusion POkemon is expressed positively in colorectal cancer cell lines and its function is negatively correlated with pl4ARF. 相似文献
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胶质瘤中p14ARF甲基化分析及其与p53表达的相关性研究 总被引:1,自引:0,他引:1
目的:探讨p14ARF甲基化与胶质瘤发生和预后的关系,及其与突变型p53 (mutant type p53,mtp53)蛋白表达的相关性.方法:采用甲基化特异性PCR(methylation specific polymerase chain reaction, MSP)法检测33例胶质瘤和12例正常脑组织中p14ARF的甲基化状况.免疫组织化学法检测58例胶质瘤和12例正常脑组织中p14ARF和mtp53蛋白的表达.结果: 胶质瘤与正常脑组织中p14ARF甲基化率分别为39.4%(13/33)和0(0/12),2组间差异有统计学意义(P<0.01).低级别组胶质瘤甲基化率(6/15)与高级别组(7/18)间差异无统计学意义(P>0.05).p14ARF甲基化情况与患者预后无明显相关性.mtp53蛋白在胶质瘤和正常脑组织中的阳性率分别为56.9%(33/58)和8.3% (1/12),2组间比较,差异有统计学意义(P<0.01),其表达在肿瘤高级别组中明显高于低级别组(P<0.05).胶质瘤中mtp53蛋白表达与p14ARF甲基化呈负相关(P<0.05).结论:p14ARF甲基化与胶质瘤发生密切相关,为胶质瘤发生的早期事件,检测p14ARF甲基化情况可作为胶质瘤早期诊断的分子生物学指标. 相似文献
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肺鳞癌、腺癌中p14 ARF基因启动子区甲基化及蛋白表达的研究 总被引:2,自引:0,他引:2
背景与目的 p14^ARF基因是新近发现的抑癌基因,其异常表达与多种人类肿瘤发生有关,启动子区异常甲基化作为p14^ARF基因失活的重要形式可能参与了肿瘤的发生。本研究通过检测肺鳞癌、腺癌中p14^ARF启动子区甲基化状态和蛋白表达,探讨p14^ARF启动子区甲基化与肺癌的关系。方法 通过免疫组织化学(IHC)、甲基化特异性PCR(MSP)和相关限制性内切酶PCR(RF-PCR)方法,检测40例肺鳞癌、腺癌组织中p14^ARF启动子区甲基化状态和蛋白表达水平。结果 癌组织及癌旁正常组织中p14^ARF启动子区甲基化阳性率分别为17.5%(7/40)和2.5%(1/40)(P-0.025)。RE-PCR检测结果相同。癌组织及癌旁正常组织中p14^ARF蛋白阳性率分别为70.0%(28/40)和95.0%(38/40)(P-0.003)。p14^ARF基因启动子区甲基化和蛋白表达均与肿瘤分期、组织类型、分化程度、淋巴结转移等临床病理特征无明显关系(P<0.05)。p14^ARF启动子区甲基化与蛋白表达呈负相关(r=-0.56,P=0.001)。结论 启动子区甲基化是p14^ARF基因失活的重要机制。p14^ARF启动子区异常甲基化可能参与了非小细胞肺癌的发生,是肺癌发生过程的早期事件。 相似文献
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目的:探讨p14ARF、MDM2和p53蛋白在脑胶质瘤组织中的表达及p14ARF-MDM2-p53通路在胶质瘤进展中的意义。方法:应用免疫组化SP法检测25例Ⅱ级和23例Ⅳ级胶质瘤组织中-p14ARF、MDM2和-p53蛋白的表达,并分析其与胶质瘤组织学分级之间的关系。结果:Ⅱ级和Ⅳ级胶质瘤中,MDM2蛋白的阳性表达率分别为24.00%(6/25)及56.52%(13/23)(P=0.021),p53蛋白的阳性表达率分别为28.00%(7/25)及60.87%(14/23)(P=0.022),二者阳性表达率均随胶质瘤恶性程度的增加而升高,Spearman等级相关分析显示,MDM2、p53的表达与胶质瘤分级呈正相关;p14ARF的阳性表达率分别为76.00%(19/25)及34.78%(8/23)(P=0.004),其阳性表达率随胶质瘤恶性程度的增加而降低,Spearman等级相关分析显示,p14ARF的表达与胶质瘤分级呈负相关(P<0.05)。结论:脑胶质瘤组织中,MDM2和p53均呈不同程度的过度表达,且随恶性程度的增加表达水平增高;而p14ARF随恶性程度的增加而表达水平降低。MDM2扩增、p53突变及p14ARF蛋白低表达均与胶质瘤的进展有关。 相似文献
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鲁建国 《国外医学(肿瘤学分册)》1998,25(3):175-176
p16,p15基因是重要的多肿瘤基因,目前研究显示其重要性已超过p53和Rb抑瘤基因,在胆胰系统肿瘤中尤为突出。本文就其在胆胰肿瘤方面的研究进展作一综述。 相似文献
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p16基因为一肿瘤抑制基因.1993年Serrano等首先克隆了p16的载体DNA(cDNA),并对其表达产物p16~(INK4)蛋白进行了分析.p16的cDNA分析表明,该基因编码一个含148个氨基酸残基分子量的15.85KD的蛋白质,称p16~(INK4).功能上p16~(INK4)能与CDK_4特异性结合,从而抑制Cyclin/CDK4激酶的活性.Kamb等研究了各型肿瘤与人类染色体9p21,从9p21上克隆出了基因MTS_1,其含1个307bp的序列,与Serrano测定的p16编码序列一致,MTS_1的全部序列是在p16cDNA上增加两个内含子,从而分隔成3个外显子:①外显子1含126bp;②外显子2含307bp;③外显子3含11bp.可见,抑癌基因p16定位于染色体9p21,同时还发现此区带存在1个与MTS_1第2个外显子高度同源的DNA序列,命名为MTS_2推测可能存在一个包括多个抑癌基因的p16家族. 相似文献
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目的探讨宫颈癌组织p14ARF蛋白的表达及其与p53表达的相关性.方法应用免疫组化方法检测p14ARF、p53基因在41例宫颈癌及20例正常宫颈组织中的表达.结果p14ARF在正常宫颈组织中不表达,41例宫颈癌中35例表达阳性,占85.4%.病理分级为G1、G2级的宫颈癌的p4ARF阳性表达率为68.4%,G3级为100%,两者比较,有显著性差异(P<0.05).宫颈癌组织中p53蛋白表达阳、阴性者中p14ARF蛋白表达阳性率分别为75.0%(12/16)和92.0%(23/25),两者比较,无显著性差异,p14ARF与p53表达不相关.结论p14ARF在宫颈癌中高表达有一定的诊断和估测预后价值,可能是宫颈癌新的肿瘤标志物. 相似文献
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目的 研究人脑胶质瘤中p14ARF蛋白的缺失情况及其与临床病理的关系。方法 采用链霉菌素 生物素 (SP)免疫组织化学法对 5 5例脑胶质瘤标本进行分析。结果 在 5 5例人脑胶质瘤标本中p14ARF缺失率为 5 0 .9%。I级 II级病例p14ARF缺失率为 32 % ,III级 IV级病例p14ARF缺失率为 6 6 .7% (P <0 .0 5 )。结论 p14ARF蛋白缺失与脑胶质瘤的发生发展有一定的相关性 ,提示p14ARF基因的失活可能是脑胶质瘤恶性演变的重要因素。 相似文献
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Objective: This study was designed to investigate promoter methylation status and protein expression of p14^ARF gene in non-small cell lung cancer, and value the role of p14^ARF promoter methylation in carcinogenesis of non-small cell lung cancer. Methods: Promoter methylation status and protein expression of p14^ARF gene in 40 cases of non-small cell lung cancer were analyzed by methylation specific polymerase china reaction (MSP), restriction enzyme-related polymerase chain reaction (RE-PCR) and immunohistochemistry (IHC). Results: The positive rates of p14^ARF promoter methylation in tumor tissues and normal tissues adjacent to cancer were 17.5% (7/40) and 2.5% (1/40) respectively. There were statistically significant differences between them, P〈0.05. The results of RE-PCR were consistent with that of MSP. The expression rate of p14^ARF protein in tumor tissues was significantly lower than that in normal tissues adjacent to cancer, p〈0.01. Promoter methylation status and protein expression of p14^ARF gene in non-small cell lung cancer showed significantly an inverse correlation (r=-0.56, P〈0.01), and both of them did not relate statistically with the clinicopathologic characteristics of patients such as histological classification, clinical stage, differentiation grade and lymph node involvement. Conclusion: Promoter methylation is a crucial mechanism of inactivation of p14^ARF gene. Promoter methylation of p14^ARF gene might he involved in carcinogenesis of non-small cell lung cancer, and is an early event in development process of non-small cell lung cancer. It might be used as a new target in gene treatments in the future. 相似文献
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目的:探讨p14ARF、p53和p21WAF1蛋白在不同级别脑胶质瘤组织中的表达及其在胶质瘤发生、发展中的生物学意义.方法:应用免疫组化SP法检测Ⅱ级和Ⅳ级胶质瘤组织中p14ARF、p53和p21WAF1蛋白的表达,并分析其与胶质瘤组织学分级之间的关系.结果:Ⅱ级和Ⅳ级胶质瘤中,p53蛋白的阳性表达率分别为28.00%(7/25)及60.87%(14/23)(P=0.022),其阳性表达率随胶质瘤恶性程度的增加而升高,Spearman等级相关分析显示,p53的表达与胶质瘤分级呈正相关(P<0.05);p21WAF1的阳性表达率分别为76.00%(19/25)及39.13%(9/23)(P=0.010) ,p14ARF的阳性表达率分别为76.00%(19/25)及 34.78%(8/23)(P=0.004),二者阳性表达率均随胶质瘤恶性程度的增加而降低,Spearman等级相关分析显示,p21WAF1、p14ARF的表达与胶质瘤分级呈负相关(P<0.05).结论:胶质瘤组织中,p53呈不同程度的过表达,且随胶质瘤恶性程度的增加而表达水平升高;p21WAF1、p14ARF随胶质瘤恶性程度的增加表达水平降低.突变型p53蛋白的过表达以及p21WAF1、p14ARF蛋白的低表达,可促进胶质瘤的发生、发展. 相似文献
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目的:探讨p14^ARF、MDM2和p53蛋白在脑胶质瘤组织中的表达及p14^ARF-MDM2-p53通路在胶质瘤进展中的意义。方法:应用免疫组化SP法检测25例Ⅱ级和23例Ⅳ级胶质瘤组织中-p14^ARF、MDM2和-p53蛋白的表达,并分析其与胶质瘤组织学分级之间的关系。结果:Ⅱ级和Ⅳ级胶质瘤中,MDM2蛋白的阳性表达率分别为24.00%(6/25)及56.52%(13/23)(P=0.021),p53蛋白的阳性表达率分别为28.00%(7/25)及60.87%(14/23)(P=0.022),二者阳性表达率均随胶质瘤恶性程度的增加而升高,Spearman等级相关分析显示,MDM2、p53的表达与胶质瘤分级呈正相关;p14^ARF的阳性表达率分别为76.00%(19/25)及34.78%(8/23)(P=0.004),其阳性表达率随胶质瘤恶性程度的增加而降低,Spearman等级相关分析显示,p14^ARF的表达与胶质瘤分级呈负相关(P〈0.05)。结论:脑胶质瘤组织中,MDM2和p53均呈不同程度的过度表达,且随恶性程度的增加表达水平增高;而p14^ARF随恶性程度的增加而表达水平降低。MDM2扩增、p53突变及p14^ARF蛋白低表达均与胶质瘤的进展有关。 相似文献
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Kohno T Yamada Y Tawara M Takasaki Y Kamihira S Tomonaga M Matsuyama T 《Leukemia research》2007,31(12):1625-1632
The INK4a/ARF locus encodes two different proteins, p16INK4a and p14ARF, which are crucial for two tumor suppressor pathways. We found that p14ARF mRNA expression was suppressed in 13 of 37 cases, among which 9 cases showed the inactivation of both of p14ARF and p16INK4a, and 4 cases showed the inactivation of p14ARF alone. The inactivation of p14ARF and the mutation of p53 are mutually exclusive. The patients with the p14ARF inactivation had shorter survival, similar to that of patients with the p53 mutation. These results indicate that the inactivation of p14ARF plays a key role in the progression of ATLL. 相似文献
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Tanaka Y Zhang SJ Terasaki H Koga H Endo S Usui H Washiyama K Kumanishi T Uematsu Y Itakura T 《Brain tumor pathology》2008,25(1):9-17
Ten glioma cell lines were examined for abnormalities of exon 1β of the p14 gene and then for abnormalities of the entire
p14 gene with the use of previous findings of other exons. Abnormalities of exon 1β and the entire p14 gene were detected
in eight of ten cases: homozygous deletion of the entire gene in six cases, hemizygous deletion of exon 1β with homozygous
deletion of downstream exons in one case, and hemizygous deletion of the entire coding region with a missense mutation (A97V)
at the C-terminal nucleolar localization domain in one case. The remaining two cases revealed tno such abnormalities. p14
gene expression was observed in the latter two cases and one case with A97V mutation in the hemizygously deleted coding region,
but not in the others, including one case with only exon 1β. In the three cases with p14 gene expression, immunocytochemistry
revealed p14 nucleolar staining, suggesting the retention of the functional activity of p14 protein and, in the case with
the A97V mutation, an insufficient mutational effect as well. The present findings of the frequent and variable p14 gene abnormalities,
including rare-type ones with or without sufficient mutational effect in glioma cell lines, might be of value for better understanding
of the p14 gene and its related pathways in glioma carcinogenesis. 相似文献