McMaster M L, Gessler M, Stanbridge E J, Weissman B E
Department of Pathology, University of North Carolina, Chapel Hill 27599, USA.
Cell Growth Differ. 1995 Dec;6(12):1609-17.
Recent studies have implicated a loss of WT1 tumor suppressor gene function in the development of Wilms' tumor (WT). To determine the potential biological consequences of WT1 inactivation in these tumors, we transfected two different splice variant forms of this gene into the pediatric kidney-derived cell line G401. Introduction of this gene caused no detectable effects on the population doubling times of the cell line; proliferative capacity in soft agar was not significantly affected. However, the expression of this gene altered the morphology of the cells in culture and caused a significant suppression of tumorigenicity in the cells. Thus, the expression of WT1 in a pediatric kidney-derived cell line lacking endogenous WT1 production caused demonstrable effects on its in vitro and in vivo growth properties. These data strengthen the concept for a central role for WT1 inactivation in the etiology of this disease.
最近的研究表明，WT1肿瘤抑制基因功能的丧失与肾母细胞瘤（WT）的发生有关。为了确定WT1失活在这些肿瘤中的潜在生物学后果，我们将该基因的两种不同剪接变体形式转染到源自小儿肾脏的细胞系G401中。该基因的导入对细胞系的群体倍增时间没有可检测到的影响；软琼脂中的增殖能力也未受到显著影响。然而，该基因的表达改变了培养细胞的形态，并显著抑制了细胞的致瘤性。因此，在缺乏内源性WT1产生的源自小儿肾脏的细胞系中WT1的表达对其体外和体内生长特性产生了明显影响。这些数据强化了WT1失活在该疾病病因中起核心作用的概念。
