Wilms tumor suppressor gene WT1 blocks cell cycle progression

我们先前证明Wilms肿瘤抑制基因WT1的过表达阻止了细胞周期从G1期向S期的进展。然而，我们也发现WT1在人类血液系统恶性肿瘤中高表达，并且WT1的表达水平与预后不良有关。此外，WT1反义寡核苷酸抑制WT1的表达可抑制白血病细胞的增殖。这些结果表明WT1对白血病细胞的增殖起重要作用。为了进一步阐明WT1在白血病细胞生长中的生物学意义，我们利用IPTG控制的表达系统在小鼠M1髓母细胞白血病细胞中过表达了外源WT1。我们发现，在M1细胞中诱导WT1会导致G1期停滞和细胞凋亡。因此，WT1的作用似乎取决于它在不同类型的白血病细胞中的表达。我们现在正试图分离其表达受WT1作用改变的cDNA。

We previously demonstrated that overexpression of the Wilms tumor suppressor gene WT1 blocks cell cycle progression from the G1 to S phase. However, we also found that WT1 is highly expressed in human hematopoietic malignancy and there exists a correlation between the levels of WT1 expression and a poor prognosis. Furthermore, suppression of WT1 expression by WT1 anti-sense oligonucleotide inhibits proliferation of leukemia cells. These results suggest that WT1 is important for the proliferation of leukemia cells. To further elucidate the biological significance of WT1 in leukemic cell growth, we overexpressed exogenous WT1 in murine M1 myeloblastic leukemia cells using the IPTG-controlled expression system. We found that induction of WT1 in M1 cells induces G1 arrest and apoptotic cell death. Thus the role of WT1 seems to be different depending on the type of leukemia cell in which it is expressed. We are now trying to isolate cDNAs the expression of which is changed by the action of WT1.