Futami Kazunobu, Ishikawa Yuichi, Goto Makoto, Furuichi Yasuhiro, Sugimoto Masanobu
GeneCare Research Institute, TECOM 2nd Building, 19-2 Kajiwara, Kamakura, Kanagawa 247-0063, Japan.
Cancer Sci. 2008 May;99(5):843-8. doi: 10.1111/j.1349-7006.2008.00778.x. Epub 2008 Feb 26.
Werner syndrome (WS) is an autosomal recessive genetic disorder causing premature aging, and WRN has been identified as the causative gene of WS. The product of the WRN gene (WRN) acts as a DNA helicase with exonuclease activity, and data have accumulated showing that the WRN gene strongly participates in carcinogenesis: (1) the normal WRN gene likely participates in the immortalization of B-lymphoblastoid cell lines through telomeric crisis caused by telomere shortening, (2) a much higher incidence of rare cancers occurs in WS patients than in other kinds of patients, and (3) levels of WRN expressed in virus-transformed cells and cancer cells are usually markedly up-regulated and are inversely correlated with the sensitivity of these cells against various genotoxins, including camptothecin. In this paper, we review the events that show a close correlation of the WRN gene and WRN with carcinogenesis and their underlying molecular mechanisms.
沃纳综合征（WS）是一种导致早衰的常染色体隐性遗传病，WRN已被确定为WS的致病基因。WRN基因的产物（WRN）作为一种具有核酸外切酶活性的DNA解旋酶，已有数据表明WRN基因在致癌过程中发挥重要作用：（1）正常的WRN基因可能通过端粒缩短引起的端粒危机参与B淋巴细胞系的永生化；（2）WS患者中罕见癌症的发病率远高于其他类型的患者；（3）病毒转化细胞和癌细胞中WRN的表达水平通常显著上调，并与这些细胞对包括喜树碱在内的各种基因毒素的敏感性呈负相关。在本文中，我们综述了显示WRN基因和WRN与致癌作用密切相关的事件及其潜在的分子机制。
