Differential regulation of the Wilms' tumor gene, WT1, during differentiation of embryonal carcinoma and embryonic stem cells

V Scharnhorst, O Kranenburg, A J van der Eb, A G Jochemsen
Cell Growth & Differentiation: the Molecular Biology Journal of the American Association for Cancer Research 1997, 8 (2): 133-43
The expression pattern of the Wilms' tumor suppressor gene, WT1, during embryonal development suggests a role for the WT1 proteins in the differentiation of specific tissues. This notion is supported by the observation that WT1 knock-out mice fall to develop kidneys and gonads. We describe here the changes in the expression and DNA binding activity of the WT1 gene product in P19 embryonal carcinoma cells and embryonic stem cells triggered to differentiate by either retinoic acid (RA) or DMSO. In exponentially growing P19 embryonal carcinoma (EC) cells, WT1 mRNA and proteins were undetectable. During RA-induced but not DMSO-induced differentiation of P19 EC cells, WT1 expression and DNA binding are strongly activated. Treatment of embryonic stem cells with RA resulted in a similar activation of WT1. Immunohistochemical analysis showed that WT1 is expressed in endodermal, glial, and epithelial cell types. In addition, DNA binding by EGR-1, a transcription factor structurally related to WT1, increased during differentiation of P19 EC and embryonic stem cells. To investigate the possible functional consequences of DNA binding by WT1, we examined the expression levels of two putative transcriptional targets of WT1, the insulin-like growth factor 1 receptor and epidermal growth factor receptor. We found that after an initial induction, decreasing expression of the insulin-like growth factor I receptor is correlated with increasing WT1 expression. Our results demonstrate that expression of WT1 is induced in specific cell types during RA-induced differentiation of P19 EC cells, reflecting the tissue-specific expression of WT1 in vivo. Therefore, we believe that P19 EC cells are a suitable system to study activation and function of WT1 during differentiation.

Full Text Links

Find Full Text Links for this Article


You are not logged in. Sign Up or Log In to join the discussion.

Trending Papers

Remove bar
Read by QxMD icon Read

Save your favorite articles in one place with a free QxMD account.


Search Tips

Use Boolean operators: AND/OR

diabetic AND foot
diabetes OR diabetic

Exclude a word using the 'minus' sign

Virchow -triad

Use Parentheses

water AND (cup OR glass)

Add an asterisk (*) at end of a word to include word stems

Neuro* will search for Neurology, Neuroscientist, Neurological, and so on

Use quotes to search for an exact phrase

"primary prevention of cancer"
(heart or cardiac or cardio*) AND arrest -"American Heart Association"