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Science 24 December 1993:
Vol. 262. no. 5142, pp. 2057 - 2059
DOI: 10.1126/science.8266105
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Articles

Science, Vol 262, Issue 5142, 2057-2059
Copyright © 1993 by American Association for the Advancement of Science

articles

WT1-mediated growth suppression of Wilms tumor cells expressing a WT1 splicing variant

DA Haber, S Park, S Maheswaran, C Englert, GG Re, DJ Hazen-Martin, DA Sens, and AJ Garvin

Laboratory of Molecular Genetics, Massachusetts General Hospital Cancer Center, Boston 02129.

A human Wilms tumor cell line (RM1) was developed to test the tumor suppressor activity of WT1, a zinc finger transcription factor that is expressed in the developing human kidney and is mutationally inactivated in a subset of Wilms tumors. Transfection of each of four wild-type WT1 isoforms suppressed the growth of RM1 cells. The endogenous WT1 transcript in these cells was devoid of exon 2 sequences, a splicing alteration that was also detected in varying amounts in all Wilms tumors tested but not in normal kidney. Production of this abnormal transcript, which encodes a functionally altered protein, may represent a distinct mechanism for inactivating WT1 in Wilms tumors.


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