Wwox的靶向缺失揭示了一种肿瘤抑制功能。
Targeted deletion of Wwox reveals a tumor suppressor function.
作者信息
Aqeilan Rami I, Trapasso Francesco, Hussain Sadiq, Costinean Stefan, Marshall Dean, Pekarsky Yuri, Hagan John P, Zanesi Nicola, Kaou Mohamed, Stein Gary S, Lian Jane B, Croce Carlo M
机构信息
Department of Molecular Virology, Immunology, and Medical Genetics, Comprehensive Cancer Center, Ohio State University, 410 West 12th Avenue, Columbus, OH 43210, USA.
出版信息
Proc Natl Acad Sci U S A. 2007 Mar 6;104(10):3949-54. doi: 10.1073/pnas.0609783104. Epub 2007 Feb 27.
The WW domain-containing oxidoreductase (WWOX) spans the second most common fragile site of the human genome, FRA16D, located at 16q23, and its expression is altered in several types of human cancer. We have previously shown that restoration of WWOX expression in cancer cells suppresses tumorigenicity. To investigate WWOX tumor suppressor function in vivo, we generated mice carrying a targeted deletion of the Wwox gene and monitored incidence of tumor formation. Osteosarcomas in juvenile Wwox(-/-) and lung papillary carcinoma in adult Wwox(+/-) mice occurred spontaneously. In addition, Wwox(+/-) mice develop significantly more ethyl nitrosourea-induced lung tumors and lymphomas in comparison to wild-type littermate mice. Intriguingly, these tumors still express Wwox protein, suggesting haploinsuffiency of WWOX itself is cancer predisposing. These results indicate that WWOX is a bona fide tumor suppressor.
含WW结构域的氧化还原酶（WWOX）跨越人类基因组中第二常见的脆性位点FRA16D，该位点位于16q23，其表达在几种人类癌症中发生改变。我们之前已经表明，癌细胞中WWOX表达的恢复会抑制肿瘤发生。为了在体内研究WWOX的肿瘤抑制功能，我们构建了携带Wwox基因靶向缺失的小鼠，并监测肿瘤形成的发生率。幼年Wwox（-/-）小鼠发生骨肉瘤，成年Wwox（+/-）小鼠发生肺乳头状癌。此外，与野生型同窝小鼠相比，Wwox（+/-）小鼠发生明显更多的乙基亚硝基脲诱导的肺肿瘤和淋巴瘤。有趣的是，这些肿瘤仍表达Wwox蛋白，表明WWOX自身的单倍剂量不足是癌症易感性的原因。这些结果表明WWOX是一种真正的肿瘤抑制因子。
Zotero 插件