Exogenous expression of WT1 gene influences U937 cell biological behaviors and activates MAPK and JAK-STAT signaling pathways.

Wilms' tumor 1 (WT1) gene plays important roles in leukemogenesis. To further explore its underlying mechanisms, we transfected two WT1 isoforms, WT1(+17AA/-KTS) and WT1(+17AA/+KTS) into U937, a WT1-null monoblastic cell line, studied their effects on migration, colony formation, apoptosis, gene expression and pertinent signaling pathways of U937 cells. The results showed that WT1(+17AA/-KTS), but not WT1(+17AA/+KTS), enhanced migration and colony forming abilities of U937 cells, and suppressed etoposide-induced U937 cell apoptosis. Transfection of WT1 isoforms activated gene expressions of chemokine, and induced up-regulation of signaling molecules involved in JAK-STAT and MAPK signaling pathways. This study showed that exogenous expression of WT1 gene remarkably affected biological behaviors of U937 cells, and these effects are possibly mediated by up-regulation of genes related to chemokine, JAK-STAT and MAPK signaling pathways.