Wilms tumor suppressor gene WT1 blocks cell cycle progression

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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.