The role of the Wilms' tumour-suppressor protein WT1 in apoptosis

Abstract

The Wilms' tumour-suppressor gene (WT1), encodes a zinc-finger transcription factor that is critical for the development of several organs, including the kidneys, gonads and spleen. Despite its identification as a tumour suppressor that plays a crucial role in the formation of a paediatric malignancy of the kidneys (Wilms' tumour), it has also emerged as an oncogenic factor influencing proliferation and apoptosis in a large variety of adult cancers. This review focuses on new insights into WT1's role in early development and its potential oncogenic role in adult cancer.

WT1 Expression in Adult Granular Cell Tumor of the Vocal Cord and Tongue

“…A nuclear-cytoplasmic shuttling is reported for WT1, which is found in cytoplasmic polysomes [7] and shown to interfere also with translation. Moreover, the extensive expression pattern of the WT1 gene product we have observed in the two examples of benign tumors, is consistent with the role of candidate-oncogene stated by Hartkamp and Roberts [8]. Interestingly, Bcl-2, direct target of WT1, is shown to increase in rhabdoid tumor cell lines with WT1 overexpression [9].…”

Membranoproliferative glomerulonephritis associated with a mutation in Wilms’ tumour suppressor gene 1

“…With no evidence of tumour persistence at the time of diagnosis of MPGN, a similar explanation cannot be invoked for our patient, despite evidence of an immune-mediated glomerulonephritis. However, the underlying mechanism may be related: WT1 plays a role in the induction of apoptosis, and failure to do so is a proposed mechanism for the persistence of nephrogenic rests and development of Wilms' tumour in patients with WT1 mutations (reviewed in [12]). Potentially, failure to induce apoptosis in aberrant, but not malignant, cells might have led to the presentation of antigens that elicited an immunological response with the formation of antigenantibody complexes in our patient.…”

The podocyte as a target: cyclosporin A in the management of the nephrotic syndrome caused by WT1 mutations

“…During mesenchymal-epithelial transition, apoptosis occurs at same time as differentiation. It has been experimentally documented that WT1 is needed to induce this transition [23]. Therefore, a decreased expression of WT1 function might result in a decreased rate of cell death and abnormal differentiation, thus contributing to the development of Wilms' tumour and WT1-GP [38].…”