人類WOX1基因位在第16對染色體易脆裂 (fragile) 的16q 23.3-24.1位點上，可轉錄轉譯出含雙色胺酸功能區氧化還原酶 (WW domain-containing oxidoreductase)。過去研究指出，在許多人類癌症，WOX1蛋白質表現量有明顯下降的情形，故WOX1一直被視為一種腫瘤抑制基因。在本研究中，我們使用WOX1基因剔除小鼠胚胎纖維母細胞 (mouse embryonic fibroblasts；MEFs) 來探討WOX1在調控細胞生長上的角色。有趣的是，我們的實驗結果發現，WOX1基因剔除的MEFs生長速度明顯比控制組MEFs快速，而且細胞周期分布情形也不相同；此外，WOX1基因剔除的MEFs、和控制組MEFs的細胞中，與調控細胞周期相關的蛋白質、以及cyclin-dependent kinase inhibitors的表現情形有顯著的差異。總結所有的實驗結果，我們的結果顯示WOX1在調控MEF細胞生長的機制中扮演重要的角色。未來，我們將繼續剖析WOX1在調控MEF細胞生長變化中的分子機制，以及WOX1在細胞生理上所扮演的角色給予定義。藉由對WOX1在細胞生長調控機制的瞭解與描述，在腫瘤形成學裡將針對WOX1的角色提供更嶄新的知識。

WW domain-containing oxidoreductase, designated WOX1, is encoded by WOX1 gene. Human WOX1 gene locates at a common fragile site on chromosome 16q 23.3-24.1. Because downregulation of WOX1 protein expression has been found in many types of human cancers, WOX1 is considered as a tumor suppressor gene. In this study, we generated gene knockout mouse embryonic fibroblasts (MEFs) to explore the potential role of WOX1 in the regulation of cell growth. Interestingly, accelerated cell growth rate and altered cell cycle distribution were detected in WOX1 gene knockout cells, as compared with the control MEFs. The expression profiles of cell cycle-related proteins and cyclin-dependent kinase inhibitors were significantly different in WOX1 gene knockout and control MEFs. In conclusion, we show here that WOX1 controls MEF cell growth. The molecular mechanism by which WOX1 regulates the phenotypic changes of MEFs and the physiological role of WOX1 in cells will be further explored. Delineating the regulation of cell growth by WOX1 will provide a novel impact on the role of WOX1 in tumorigenesis.

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