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转化的大鼠胚胎成纤维细胞系与p53val135功能关系的研究 总被引:7,自引:4,他引:3
A1-5是一株典型的温度敏感的p53^val135细胞系,许多实验室用它来研究p53的功能,我们首次报道了A1-5细胞表现出非常强的抗辐射性并伴随不同寻常强的G2延迟效应,B4是另一株温度敏感的p53^val135细胞系,A1-5与B4细胞都 是来源于同样的原代转化的大鼠胚胎成纤维细胞系,只是来自不同的转染实验,本阐明了A1-5细胞非常强的抗辐射性及不同寻常强的G2停滞效应与p53val135的功能无关,A1-5细胞系具有的特殊表型是研究放射敏感性新性质的独特的模型。 相似文献
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On the expression of the p53 protein in human cancer 总被引:5,自引:0,他引:5
D. P. Lane 《Molecular biology reports》1994,19(1):23-29
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Phatak P Selvi SK Divya T Hegde AS Hegde S Somasundaram K 《Journal of biosciences》2002,27(7):673-678
Alterations in the tumour suppressorp53 gene are among the most common defects seen in a variety of human cancers. In order to study the significance of thep53 gene in the genesis and development of human glioma from Indian patients, we checked 44 untreated primary gliomas for mutations
in exons 5–9 of thep53 gene by PCR-SSCP and DNA sequencing. Sequencing analysis revealed six missense mutations. The incidence of p53 mutations
was 13⋅6% (6 of 44). All the six mutations were found to be located in the central core domain of p53, which carries the sequence-specific
DNA-binding domain. These results suggest a rather low incidence but a definite involvement of p53 mutations in the gliomas
of Indian patients. 相似文献
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The research evaluated the effect of Δ133p53 on the chemosensitivity of lung adenocarcinoma cell line H1299. By this study, the drug‐resistant molecular marker and a new target for cancer therapy could be provided. Δ133p53 or negative control plasmid were transferred into H1299 cells by lentivirus vector. The expression of Δ133p53 in transfected cells was examined using immunofluorescence. The 3‐(4,5‐dimethylthiazol‐2‐yl)‐2,5‐diphenyl tetrazolium bromide (MTT) method and colony formation test were applied to detect drug sensitivity after cisplatin or 5‐fluorouracil (5‐FU) treatment. After cisplatin (CDDP)/FU treatment, MTT assay demonstrated that the inhibition rate of H1299/Δ133p53 cell was reduced compared with that of the H1299 and H1299/NEG cells at the same concentration of drug. The 50% inhibitory concentrations (IC 50) of CDDP and 5‐FU rose by 36.1 and 30.2%, respectively (P < 0.05). The colony formation assay suggested that the cell proliferation ability of H1299/Δ133p53 cell was prominently increased when compared with that of control group H1299 and H1299 /NEG cells (P < 0.05). The present study demonstrated that the transfection of the Δ133p53 gene in H1299 cells led to the reduction of chemosensitivity. 相似文献
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Ottaggio L Campomenosi P Fronza G Menichini P Miele M Moro F Viaggi S Zunino A Abbondandolo A 《Journal of cellular biochemistry》2006,98(6):1689-1700
We have previously described a methotrexate-resistant cell line (MTX M) characterized by amplified dihydrofolate reductase (DHFR) genes, cytoplasmic p53 localization, and p53 stable tetramers. To investigate the p53 functionality in MTX M, the effect of chemical/physical agents was studied. In MTX M cells, DNA damage did not induce p53 or mdm-2 protein, while in the parental V79 cells, a residual p53 activity was found. cDNA sequencing showed that V79 and MTX M cells share the same mutations, indicating that the complete loss of p53 function in MTX M cells was due to cytoplasmic sequestration of a mutated p53 with residual activity. In Chinese hamster, both p53 and DHFR genes map on short arm of chromosome 2 suggesting that p53 itself might be amplified. However, fluorescence in situ hybridization with a hamster p53 probe showed only a single signal. Thus, the presence of p53 stable tetramers in MTX M cells, although correlated with DNA amplification, could not be the consequence of either p53 or DHFR gene amplification. Expression of a C-terminal human p53 peptide does not induce p53 nuclear accumulation, indicating that the cytoplasmic localization is due to a mechanism different from that already described in cancer cell lines. Treatments with Sodium Butyrate induced beta-tubulin polymerization, but did not apparently organize a normal microtubule network, which is shown to be important for the p53 localization. Our data indicated that in MTX M cells, p53 is sequestered in the cytoplasm by a novel mechanism that abrogates p53 residual function. 相似文献
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Enhanced gene transfer and cell death following p53 gene transfer using photochemical internalisation of glucosylated PEI-DNA complexes 总被引:2,自引:0,他引:2
Ndoye A Merlin JL Leroux A Dolivet G Erbacher P Behr JP Berg K Guillemin F 《The journal of gene medicine》2004,6(8):884-894
BACKGROUND: p53 is frequently mutated in many cancers including human head and neck squamous cell carcinoma and pancreatic cancer. In tumor models, wild-type (wt) p53 gene transfer induces apoptosis and tumor regression in vivo, justifying the extensive clinical investigation of p53 gene therapy. METHODS: p53 nonviral-mediated gene transfer was achieved using glucosylated polyethylenimine (PEI) in conjunction with photochemical internalisation (PCI). Experimental conditions were optimised using the green fluorescent protein (GFP) as a reporter. p53 gene transfer was then evaluated using semi-quantitative RT-PCR in p53-deleted PANC3 and p53-mutated FaDu cell lines. Following gene transfer, induction of apoptosis was investigated using phosphatidylserine externalisation and nuclear fragmentation assays. Induction of long-term cell death was analysed using colony-forming assays. RESULTS: PCI was found to enhance GFP gene transfer after 48 h in both cell lines. Whether using glucosylated-PEI alone or associated with PCI, p53 gene transfer was achieved with subsequent recovery of p53 mRNA expression in PANC3 cells and a significant 4-fold increase in p53 mRNA expression in FaDu cells. PCI was found to further enhance p53 mRNA expression by 2.3-fold in PANC3 cells. Spontaneous induction of apoptosis following wt-p53 gene transfer was achieved in both cell lines. PCI was found to enhance apoptosis up to levels similar to those achieved with chemotherapy. As a consequence, long-term cell death was significantly enhanced after wt-p53 gene transfer when PCI was used in both cell lines, yielding up to 60% cell death. CONCLUSIONS: PCI increases glucosylated-PEI-mediated p53 gene transfer, apoptosis as well as cell death in mutant p53 human cancer cells. 相似文献
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目的:构建DEK的pcDNA3-Flag表达载体,研究其对抑癌基因p53启动子活性的影响。方法:以乳腺文库为模板,PCR扩增DEK编码序列,克隆到pcDNA3-Flag载体,构建成pcDNA3-Flag-DEK,转染293T细胞,Western印迹鉴定peDNA3-Flag载体介导的DEK的表达,萤光素酶报告基因活性实验研究DEK对p53启动子活性的影响。结果:双酶切实验证实得到pcDNA3-Flag-DEK阳性克隆;Western印迹实验发现DEK在293T细胞内表达;转录活性实验表明在ZR75-1乳腺癌细胞中,DEK呈剂量依赖性抑制p53启动子的活性。结论:构建了DEK的真核表达载体,并发现此表达载体能在ZR75-1乳腺癌细胞中抑制p53启动子活性。 相似文献
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Xiao-Yan Gao Ying-Yu Lai Xue-Shan Luo De-Wei Peng Qiao-Qiao Li Hui-Shan Zhou Yu-Mei Xue Hui-Ming Guo Jun-Fei Zhao Hui Yang Su-Juan Kuang Zhao-Yu Wang Meng-Zhen Zhang Chun-Yu Deng Shu-Lin Wu Fang Rao 《Aging cell》2023,22(1):e13743
Atrial fibrosis induced by aging is one of the main causes of atrial fibrillation (AF), but the potential molecular mechanism is not clear. Acetyltransferase p300 participates in the cellular senescence and fibrosis, which might be involved in the age-related atrial fibrosis. Four microarray datasets generated from atrial tissue of AF patients and sinus rhythm (SR) controls were analyzed to find the possible relationship of p300 (EP300) with senescence and fibrosis. And then, biochemical assays and in vivo electrophysiological examination were performed on older AF patients, aging mice, and senescent atrial fibroblasts. The results showed that (1) the left atrial tissues of older AF patients, aging mouse, and senescence human atrial fibroblasts had more severe atrial fibrosis and higher protein expression levels of p300, p53/acetylated p53 (ac-p53)/p21, Smad3/p-Smads, and fibrosis-related factors. (2) p300 inhibitor curcumin and p300 knockdown treated aging mouse and senescence human atrial fibroblasts reduced the senescence ratio of atrial fibroblasts, ameliorated the atrial fibrosis, and decreased the AF inducibility. In contrast, over-expression of p300 can lead to the senescence of atrial fibroblasts and atrial fibrosis. (3) p53 knockdown decreased the expression of aging and fibrosis-related proteins. (4) Co-immunoprecipitation and immunofluorescence showed that p53 forms a complex with smad3 and directly regulates the expression of smad3 in atrial fibroblasts. Our findings suggest that the mechanism of atrial fibrosis induced by aging is, at least, partially dependent on the regulation of p300, which provides new sights into the AF treatment, especially for the elderly. 相似文献
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Complicating the role of p53 in aging 总被引:2,自引:0,他引:2