Al. Menke et al., WILMS-TUMOR-1 SPLICE VARIANTS HAVE OPPOSITE EFFECTS ON THE TUMORIGENICITY OF ADENOVIRUS-TRANSFORMED BABY-RAT KIDNEY-CELLS, Oncogene, 12(3), 1996, pp. 537-546
The Wilms' Tumor 1 gene (WT1) encodes a transcription factor of the zi
nc-finger family, As a result of alternative RNA splicing, the gene ca
n be expressed as four polypeptides which differ in the presence or ab
sence of two stretches of amino acids: one of 17 residues (17aa) just
N-terminal of the four zinc-fingers and of three residues (K-T-S) betw
een zinc finger 3 and 4. In this study, four human cDNA constructs enc
oding the Wilms' tumor 1 splice variants were stably transfected into
adenovirus-transformed baby rat kidney (Ad-BRK) cells. The in vivo pro
duced WT1 proteins that lacked the KTS residues were found to bind eff
iciently to both the Egr-1 consensus sequence and the recently describ
ed WTE DNA sequence, as determined by electrophoretic mobility shift a
ssays. Our studies show distinct effects of the different WT1 isoforms
. Expression of the WT1 (-/+) protein, lacking the 17aa insert, strong
ly suppressed the tumorigenic phenotype of the Ad-BRK cells. Intriguin
gly, expression of the WT1 (-/-) protein, lacking both inserts, increa
sed the tumor growth rate. In contrast to the growth in vivo, the grow
th rate of the transfectants in tissue culture is not influenced by an
y of the WT1 isoforms. However, the suppression of tumorigenicity appe
ars to be correlated with a reduced ability of the cells to grow in se
rum-free medium.