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多形性胶质母细胞瘤中 WW0X 表达与增殖和凋亡的相关性的分子分析。

Molecular analysis of WWOX expression correlation with proliferation and apoptosis in glioblastoma multiforme.

机构信息

Department of Molecular Cancerogenesis, Medical University of Lodz, Mazowiecka St 6/8, 92-215 Lodz, Poland.

出版信息

J Neurooncol. 2011 Jan;101(2):207-13. doi: 10.1007/s11060-010-0254-1. Epub 2010 Jun 10.

DOI:10.1007/s11060-010-0254-1
PMID:20535528
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC2996532/
Abstract

Glioblastoma multiforme is the most common type of primary brain tumor in adults. WWOX is a tumor suppressor gene involved in carcinogenesis and cancer progression in many different neoplasms. Reduced WWOX expression is associated with more aggressive phenotype and poor patient outcome in several cancers. We investigated alternations of WWOX expression and its correlation with proliferation, apoptosis and signal trafficking in 67 glioblastoma multiforme specimens. Moreover, we examined the level of WWOX LOH and methylation status in WWOX promoter region. Our results suggest that loss of heterozygosity (relatively frequent in glioblastoma multiforme) along with promoter methylation may decrease the expression of this tumor suppressor gene. Our experiment revealed positive correlations between WWOX and Bcl2 and between WWOX and Ki67. We also confirmed that WWOX is positively correlated with ErbB4 signaling pathway in glioblastoma multiforme.

摘要

多形性胶质母细胞瘤是成人中最常见的原发性脑肿瘤。WWOX 是一种肿瘤抑制基因,参与多种不同肿瘤的致癌作用和癌症进展。在几种癌症中,WWOX 表达降低与侵袭性表型和患者预后不良相关。我们研究了 67 例多形性胶质母细胞瘤标本中 WWOX 表达的改变及其与增殖、凋亡和信号转导的相关性。此外,我们还检查了 WWOX 基因缺失和启动子区甲基化状态。我们的结果表明,杂合性缺失(在多形性胶质母细胞瘤中相对常见)以及启动子甲基化可能会降低这种肿瘤抑制基因的表达。我们的实验还揭示了 WWOX 与 Bcl2 之间以及 WWOX 与 Ki67 之间呈正相关。我们还证实,在多形性胶质母细胞瘤中,WWOX 与 ErbB4 信号通路呈正相关。

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Molecular analysis of WWOX expression correlation with proliferation and apoptosis in glioblastoma multiforme.多形性胶质母细胞瘤中 WW0X 表达与增殖和凋亡的相关性的分子分析。
J Neurooncol. 2011 Jan;101(2):207-13. doi: 10.1007/s11060-010-0254-1. Epub 2010 Jun 10.
2
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本文引用的文献

1
WWOX, the tumour suppressor gene affected in multiple cancers.WWOX,一种在多种癌症中受到影响的肿瘤抑制基因。
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2
WWOX gene expression abolishes ovarian cancer tumorigenicity in vivo and decreases attachment to fibronectin via integrin alpha3.WWOX基因表达可消除卵巢癌在体内的致瘤性,并通过整合素α3降低对纤连蛋白的附着。
Cancer Res. 2009 Jun 1;69(11):4835-42. doi: 10.1158/0008-5472.CAN-08-2974. Epub 2009 May 19.
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Targeted ablation of the WW domain-containing oxidoreductase tumor suppressor leads to impaired steroidogenesis.对含WW结构域的氧化还原酶肿瘤抑制因子进行靶向消融会导致类固醇生成受损。
Endocrinology. 2009 Mar;150(3):1530-5. doi: 10.1210/en.2008-1087. Epub 2008 Oct 30.
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HER4 intracellular domain (4ICD) activity in the developing mammary gland and breast cancer.HER4细胞内结构域(4ICD)在乳腺发育和乳腺癌中的活性。
J Mammary Gland Biol Neoplasia. 2008 Jun;13(2):247-58. doi: 10.1007/s10911-008-9076-6. Epub 2008 May 13.
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MethylScreen: DNA methylation density monitoring using quantitative PCR.甲基化筛选:利用定量PCR监测DNA甲基化密度
Biotechniques. 2007 Nov;43(5):683-93. doi: 10.2144/000112597.
6
Association of Wwox with ErbB4 in breast cancer.乳腺癌中WWOX与ErbB4的关联。
Cancer Res. 2007 Oct 1;67(19):9330-6. doi: 10.1158/0008-5472.CAN-07-2147.
7
WWOX, a new potential tumor suppressor gene.WWOX,一种新的潜在肿瘤抑制基因。
Biomed Pap Med Fac Univ Palacky Olomouc Czech Repub. 2007 Jun;151(1):11-5. doi: 10.5507/bp.2007.002.
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WWOX in biological control and tumorigenesis.WWOX在生物调控与肿瘤发生中的作用
J Cell Physiol. 2007 Aug;212(2):307-10. doi: 10.1002/jcp.21099.
9
Genetic pathways to primary and secondary glioblastoma.原发性和继发性胶质母细胞瘤的遗传途径。
Am J Pathol. 2007 May;170(5):1445-53. doi: 10.2353/ajpath.2007.070011.
10
Inhibition of breast cancer cell growth in vitro and in vivo: effect of restoration of Wwox expression.体外和体内对乳腺癌细胞生长的抑制作用:Wwox表达恢复的影响
Clin Cancer Res. 2007 Jan 1;13(1):268-74. doi: 10.1158/1078-0432.CCR-06-2038.