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Anticancer research

The Wilms' tumor suppressor WT1 inhibits malignant progression of neoplastigenic mammary epithelial cells.


PMID 18751389

Abstract

The Wilms' tumor suppressor gene, wt1, encodes a zinc-finger protein, WT1, that functions as a transcription regulator. Previous studies have suggested a contradictory role for WT1 in breast cancer development. MCF10AT3B cells, a cell line derived from a xenograft model of progressive human proliferative breast disease, were used to study WT1 function in early development of breast cancer. A stable cell line was established from MCF10AT3B cells that ectopically expressed the Wilms' tumor suppressor, WT1. Western blot analysis, in vitro and in vivo growth assays were used to study the effects of constitutive WT1 expression on malignant progression of MCF10AT3B cells. WT1 expression had a profound effect on several aspects of the cell cycle machinery and inhibited estrogen-stimulated and nonstimulated cell growth in vitro. In nude mice, WT1 expression strongly suppressed estrogen-stimulated tumorigenesis of neoplastigenic MCF10AT3B cells. WT1 plays an important role in maintaining normal growth of mammary epithelial cells and dysregulated WT1 expression may contribute to breast cancer development.