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Publication : The tumor suppressor gene WT1 inhibits ras-mediated transformation.

First Author  Luo XN Year  1995
Journal  Oncogene Volume  11
Issue  4 Pages  743-50
PubMed ID  7651738 Mgi Jnum  J:28327
Mgi Id  MGI:75947 Citation  Luo XN, et al. (1995) The tumor suppressor gene WT1 inhibits ras-mediated transformation. Oncogene 11(4):743-50
abstractText  Wilms' tumor belongs to a small group of pediatric neoplasms that have served as paradigms of human cancers in which recessive mutations play a primary role in tumorigenesis. WT1 is a candidate tumor suppressor gene that is mutationally inactivated in a proportion of both familial and sporadic Wilms' tumors. Recent studies demonstrated that WT1 can partially suppress growth of a Wilms' tumor cell line in vitro and in vivo. We investigated the ability of WT1 to inhibit the expression of the transformed phenotype in non-Wilms' tumor cells. The expression of WT1 cDNA in ras-transformed NIH3T3 cells yielded large, flat cells that exhibited complete contact-inhibition. These morphologic changes were associated with decreased proliferation, suppression of clonogenicity in soft agar and inhibition of tumor growth in nude mice. Moreover, expression of WT1 in non-transformed NIH3T3 cells resulted in similar morphologic changes and profound resistance to transformation by an activated ras oncogene. These studies suggest that tumor inhibition by WT1 in these cells may be achieved by interference with the ras-mediated signalling pathway.
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