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四种人髓母细胞瘤衍生细胞系中的p53表达

p53 expression in four human medulloblastoma-derived cell lines.

作者信息

Srinivasan J, Berger M S, Silber J R

机构信息

Department of Neurological Surgery, University of Washington Medical Center, Seattle 98195, USA.

出版信息

Childs Nerv Syst. 1996 Feb;12(2):76-80. doi: 10.1007/BF00819500.

DOI:10.1007/BF00819500
PMID:8674085
Abstract

p53 is a tumor suppressor gene found on the short arm of chromosome 17. Loss of one p53 allele and alteration of the other is found in a variety of tumors, including highgrade glial tumors. Point mutations in the remaining allele occur in a highly conserved region of the gene encompassing exons 5-8. Although 40-50% of medulloblastomas lose sequences on the short arm of chromosome 17, alteration of p53 in these tumors is infrequent. To further characterize genetic alteration of p53 in medulloblastoma, we performed a mutational analysis of four medulloblastoma-derived cell lines established by our laboratory. Using two variable-number tandem repeat markers which map distally to p53, we found evidence indicating loss of sequences on the distal end of chromosome 17p in all four lines. However, no gross alterations of the p53 gene were detected. Northern analysis revealed expression of equivalent amounts of full-length p53 messenger RNA in each cell line. Using the polymerase chain reaction to amplify exons 5-8 of the p53 gene, we directly sequenced the amplified fragments and detected no mutations in any of the cell lines. Our results demonstrate that loss of p53 function through gene deletion and/or recessive mutation is not required for growth in our cell lines.

摘要

p53是一种肿瘤抑制基因,位于17号染色体短臂上。在包括高级别胶质瘤在内的多种肿瘤中都发现一个p53等位基因缺失,另一个发生改变。剩余等位基因的点突变发生在该基因包含外显子5 - 8的高度保守区域。虽然40% - 50%的髓母细胞瘤在17号染色体短臂上存在序列缺失,但这些肿瘤中p53的改变并不常见。为了进一步明确髓母细胞瘤中p53的基因改变情况,我们对本实验室建立的4个髓母细胞瘤衍生细胞系进行了突变分析。使用两个定位于p53远端的可变数目串联重复标记,我们发现所有4个细胞系中均有17号染色体短臂远端序列缺失的证据。然而,未检测到p53基因的明显改变。Northern印迹分析显示每个细胞系中全长p53信使核糖核酸的表达量相当。使用聚合酶链反应扩增p53基因的外显子5 - 8,我们对扩增片段进行直接测序,未在任何细胞系中检测到突变。我们的结果表明,在我们的细胞系中,通过基因缺失和/或隐性突变导致p53功能丧失并非细胞生长所必需。

相似文献

1
p53 expression in four human medulloblastoma-derived cell lines.四种人髓母细胞瘤衍生细胞系中的p53表达
Childs Nerv Syst. 1996 Feb;12(2):76-80. doi: 10.1007/BF00819500.
2
Infrequent p53 gene mutations in medulloblastomas.髓母细胞瘤中p53基因罕见突变。
Cancer Res. 1991 Sep 1;51(17):4721-3.
3
p53 gene mutation and mdm2 gene amplification are uncommon in medulloblastoma.p53基因突变和mdm2基因扩增在髓母细胞瘤中并不常见。
Cancer Res. 1994 Nov 1;54(21):5649-51.
4
Chromosome 17p deletions and p53 mutations in renal cell carcinoma.肾细胞癌中的17号染色体短臂缺失和p53基因突变
Cancer Res. 1993 Jul 1;53(13):3092-7.
5
p53 gene mutations in medulloblastoma. Immunohistochemistry, gel shift analysis, and sequencing.髓母细胞瘤中的p53基因突变。免疫组织化学、凝胶迁移分析及测序
Diagn Mol Pathol. 1993 Mar;2(1):23-8.
6
Evidence for a gene on 17p13.3, distal to TP53, as a target for allele loss in breast tumors without p53 mutations.在17p13.3上,位于TP53远端的一个基因作为无p53突变的乳腺肿瘤中等位基因缺失靶点的证据。
Cancer Res. 1994 Aug 1;54(15):4200-6.
7
Genetic alterations of the p53 gene are a feature of malignant mesotheliomas.p53基因的遗传改变是恶性间皮瘤的一个特征。
Cancer Res. 1991 Oct 1;51(19):5410-6.
8
Involvement of multiple chromosome 17p loci in medulloblastoma tumorigenesis.
Am J Hum Genet. 1992 Mar;50(3):584-9.
9
p53 gene expression in medulloblastoma by quantitative polymerase chain reaction.通过定量聚合酶链反应检测髓母细胞瘤中的p53基因表达
Diagn Mol Pathol. 1992 Mar;1(1):36-44. doi: 10.1097/00019606-199203000-00006.
10
Evidence for the involvement of a potential second tumor suppressor gene on chromosome 17 distinct from p53 in malignant astrocytomas.在恶性星形细胞瘤中,17号染色体上存在一个不同于p53的潜在第二肿瘤抑制基因参与其中的证据。
Cancer Res. 1992 Dec 1;52(23):6716-21.

本文引用的文献

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Doing the right thing: feedback control and p53.做正确的事:反馈控制与p53
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Amplification and overexpression of the MDM2 gene in a subset of human malignant gliomas without p53 mutations.在一部分无p53突变的人类恶性胶质瘤中,MDM2基因的扩增和过表达。
Cancer Res. 1993 Jun 15;53(12):2736-9.
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Thymocyte apoptosis induced by p53-dependent and independent pathways.由p53依赖和非依赖途径诱导的胸腺细胞凋亡。
Nature. 1993 Apr 29;362(6423):849-52. doi: 10.1038/362849a0.
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p53 is required for radiation-induced apoptosis in mouse thymocytes.p53是小鼠胸腺细胞辐射诱导凋亡所必需的。
Nature. 1993 Apr 29;362(6423):847-9. doi: 10.1038/362847a0.
5
11th Ernst Klenk Lecture. The p53 tumor suppressor gene and product.第11届恩斯特·克伦克讲座。p53肿瘤抑制基因与产物
Biol Chem Hoppe Seyler. 1993 Apr;374(4):227-35.
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The p53 tumor suppressor protein: meeting review.p53肿瘤抑制蛋白:会议综述
Genes Dev. 1993 Apr;7(4):529-34. doi: 10.1101/gad.7.4.529.
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Frequency of p53 tumor suppressor gene mutations in human primary brain tumors.人类原发性脑肿瘤中p53肿瘤抑制基因突变的频率。
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UV irradiation stimulates levels of p53 cellular tumor antigen in nontransformed mouse cells.紫外线照射可刺激未转化小鼠细胞中p53细胞肿瘤抗原的水平。
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