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WWOX基因和肿瘤的研究进展

Advances of research on WWOX gene and cancer
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摘要 WWOX是公认的抑癌基因之一，与肿瘤坏死因子、p53蛋白及诸多其它信号通路蛋白相互作用而诱导细胞凋亡，同时WWOX的活性可被E2F-1、c-Jun氨基末端激酶1（JNK1）等因子调控。在肿瘤中WWOX失活主要是频发甲基化修饰、6～8外显子的丢失、LOH及WWOX蛋白表达的降低。增加该基因在肿瘤细胞和癌症患者中的表达将抑制肿瘤的发生发展。目前该基因的信号通路过程还不明了，有待于进一步的研究。 WWOX gene is universally regarded as one of the tumor suppressor genes. It interacts with tumor necrosis factor, p53 and other protein to induce cell apoptosis. Meanwhile, the activity of WWOX gene can be regulated by E2F-1 , c-Jun NH（2）-terminal protein kinase and other factors. The disorders of WWOX gene in tumor mainly include DNA methylation, loss of exon 6 - 8, LOH and decreasing of the protein expression. Increasing WWOX expression in tumor cell and cancer＇ patients can suppress oceurrence anti development of tumor. At present, the signal transduction pathway is remained unknown and ,reeds further research.
作者 吴俊杰 李强
机构地区 第二军医大学附属长海医院呼吸内科
出处 《国际内科学杂志》 CAS 2008年第6期364-367,共4页 International Journal of Internal Medicine
关键词 WWOX FOR 脆性位点 抑癌基因 肿瘤 WWOX FOR Fragile site Tumor suppressor gene Tumor
分类号 R730.231 [医药卫生—肿瘤]
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参考文献28

  • 1Bednarek AK, Laflin KJ, Daniel RL, et al. WWOX, a novel WW domain-containing protein mapping to human chromosome 16q23.3-24. 1, a region frequently affected in breast cancer. Cancer Res, 2000,60 ( 8 ) :2140-2145.
  • 2Ried K, Finnis M, Hobson L,et al. Common chromosomal fragile site FRAI6D sequence: identification of the FOR gene spanning FRAI6D and homozygous deletions and translocation breakpoints in cancer cells. Hum Mol Genet, 2000, 9(11) :1651-1663.
  • 3Bednarek AK, Keck-Waggoner CL, Daniel RL, et al. WWOX, the FRA16 D gene, behaves as a suppressor of tumor growth. Cancer Res, 2001, 61 (22) : 8068-8073.
  • 4Chang NS, Hsu LJ, Lin YS, et al. WW domain-containing oxidoreductase: a candidate tumor suppressor. Trends Mol Med, 2007, 13( 1 ) :12-22.
  • 5Aqeilan RI, Pekarsky Y, Herrero JJ, et al. Functional association between Wwox tumor suppressor protein and p73, ap53 homolog. Proc Natl Acad Sci U S A, 2004, 101 (13) : 4401-4406.
  • 6Ludes-Meyers JH, Kil H, Bednarek AK,et al. WWOX binds the specific proline-rich ligand PPXY: identification of candidate interacting proteins. Oneogene, 2004, 23 ( 29 ) : 5049- 5055.
  • 7Chang NS, Pratt N, Heath J, et al. Hyaluronidase induetion of a WW domain-containing oxidoreduetase that enhances tumor necrosis factor eytotoxieity. J Biol Chem, 2001, 276 (5) : 3361-3370.
  • 8Chang NS, Doherty J, Ensign A, et al. WOX1 is essential for tumor necrosis factor-, UV light-, staurosporine-, and p53-mediated cell death, and its tyrosine 33-phosphorylated form binds and stabilizes serine 46-phosphorylated p53. J Biol Chem, 2005,280 (52) : 43100-43108.
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国际内科学杂志
2008年 第6期

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