Cell Growth & Differentiation, Vol 5, Issue 6 677-686, Copyright © 1994 by American Association of Cancer Research

ARTICLES

Wilms' tumor gene, WT1, mRNA is down-regulated during induction of erythroid and megakaryocytic differentiation of K562 cells

SA Phelan, C Lindberg and KM Call
Department of Molecular and Cellular Toxicology, Harvard School of Public Health, Boston, Massachusetts 02115.

Evidence implicates the product of the Wilms' tumor suppressor gene, WT1, in proliferation and differentiation of target tissues during development. Study of the regulation of other tumor suppressor genes during these processes has been instrumental in defining their interactions and functions. In this study, we performed experiments to assess the suitability of the human K562 erythroleukemia cell line for studying the WT1 gene during differentiation. We predicted that WT1 mRNA would be decreased during induction of differentiation of K562 cells based on observations of decreased WT1 mRNA during kidney development and in differentiated Wilms' tumors and leukemias. Accordingly, we found that WT1 mRNA was down-regulated in K562 cells during induction of erythroid and megakaryocytic differentiation by sodium butyrate and 12-O-tetradecanoylphorbol-13-acetate, respectively. Down-regulation of WT1 mRNA was not a generalized phenomenon of growth inhibition. WT1 mRNA was not down-regulated when 12-O-tetradecanoylphorbol-13-acetate-induced differentiation was blocked by bryostatin-1. During 12-O-tetradecanoylphorbol-13-acetate treatment, the decrease in WT1 mRNA was rapid (within 5 min), continuous, and occurred, at least in part, posttranscriptionally. An analysis of the 5' flanking region and transcription initiation sites of the human WT1 gene also was performed. Our data suggest that K562 cells will be a valuable system for unraveling signal transduction pathways by which WT1 is regulated and for investigating the interactions and role of WT1 in differentiation.

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