Murata Y, Kudoh T, Sugiyama H, Toyoshima K, Akiyama T
Department of Oncogene Research, Institute for Microbial Diseases, Osaka University, Suita, Japan.
FEBS Lett. 1997 Jun 2;409(1):41-5. doi: 10.1016/s0014-5793(97)00477-8.
WT1 was isolated as a tumor suppressor gene of Wilms tumor. However, high expression of WT1 correlates with poor prognosis in acute leukemia. In addition suppression of WT1 expression by WT1 anti-sense oligonucleotide inhibits proliferation of leukemia cells, suggesting that WT1 is important for their proliferation. To further elucidate the biological significance of WT1 in leukemic cell growth, we overexpressed exogenous WT1 in murine M1 myeloblastic leukemia cells using the isopropyl-beta-D-thiogalactoside (IPTG)-controlled expression system. We found that induction of one splicing variant of WT1 [WT1-17AA(+)-KTS(-)] in M1 cells induces cell cycle arrest and apoptotic cell death. These results suggest that the role of WT1 is different depending on the type of leukemia cell in which it is expressed.
WT1最初作为肾母细胞瘤的肿瘤抑制基因被分离出来。然而，WT1的高表达与急性白血病的不良预后相关。此外，WT1反义寡核苷酸抑制WT1表达可抑制白血病细胞的增殖，这表明WT1对其增殖很重要。为了进一步阐明WT1在白血病细胞生长中的生物学意义，我们使用异丙基-β-D-硫代半乳糖苷（IPTG）控制的表达系统在小鼠M1骨髓性白血病细胞中过表达外源性WT1。我们发现，在M1细胞中诱导WT1的一种剪接变体[WT1-17AA(+)-KTS(-)]会诱导细胞周期停滞和凋亡性细胞死亡。这些结果表明，WT1的作用因其所表达的白血病细胞类型而异。
