A tumor suppressor and oncogene: the WT1 story.

The Wilms' tumor 1 (WT1) gene encodes a transcription factor important for normal cellular development and cell survival. The initial discovery of WT1 as the causative gene in an autosomal-recessive condition identified it as a tumor suppressor gene whose mutations are associated with urogenital disease and the development of kidney tumors. However, this view is not in keeping with the frequent finding of wild-type, full-length WT1 in human leukemia, breast cancer and several other cancers including the majority of Wilms' tumors. Rather, these observations suggest that in those conditions, WT1 has an oncogenic role in tumor formation. In this review, we explore the literature supporting both views of WT1 in human cancer and in particular human leukemias. To understand the mechanism by which WT1 can do this, we will also examine its functional activity as a transcription factor and the influence of protein partners on its dual behavior.