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PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
2
pubmed:dateCreated
1997-5-6
pubmed:abstractText
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.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Feb
pubmed:issn
1044-9523
pubmed:author
pubmed:issnType
Print
pubmed:volume
8
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
133-43
pubmed:dateRevised
2009-11-19
pubmed:meshHeading
pubmed-meshheading:9040935-Blotting, Western, pubmed-meshheading:9040935-Carcinoma, Embryonal, pubmed-meshheading:9040935-Cell Differentiation, pubmed-meshheading:9040935-Cell Line, pubmed-meshheading:9040935-DNA-Binding Proteins, pubmed-meshheading:9040935-Dimethyl Sulfoxide, pubmed-meshheading:9040935-Early Growth Response Protein 1, pubmed-meshheading:9040935-Gene Expression Regulation, Developmental, pubmed-meshheading:9040935-Genes, Wilms Tumor, pubmed-meshheading:9040935-Humans, pubmed-meshheading:9040935-Immediate-Early Proteins, pubmed-meshheading:9040935-Neuroglia, pubmed-meshheading:9040935-RNA, Messenger, pubmed-meshheading:9040935-Receptor, IGF Type 1, pubmed-meshheading:9040935-Stem Cells, pubmed-meshheading:9040935-Transcription Factors, pubmed-meshheading:9040935-Tretinoin, pubmed-meshheading:9040935-WT1 Proteins
pubmed:year
1997
pubmed:articleTitle
Differential regulation of the Wilms' tumor gene, WT1, during differentiation of embryonal carcinoma and embryonic stem cells.
pubmed:affiliation
Laboratory of Molecular Carcinogenesis, Sylvius Laboratories, Leiden University, The Netherlands.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't