WT1 induces expression of insulin-like growth factor 2 in Wilms' tumor cells

The Wilms' tumor suppressor gene WT1 encodes a zinc finger transcription factor, whose expression inhibits the growth of the RM1 Wilms' tumor cell line. Transient transfection of WT1 constructs into 3T3 or 293 cells results in transcriptional repression of a number of cotransfected promote...

Full description

Saved in:
Bibliographic Details
Published in:Cancer research (Chicago, Ill.) Ill.), 1995-10, Vol.55 (20), p.4540-4543
Main Authors: NICHOLS, K. E, RE, G. G, YU XIN YAN, GARVIN, A. J, HABER, D. A
Format: Article
Language:English
Subjects:
Base Sequence
Biological and medical sciences
DNA-Binding Proteins - physiology
Gene Expression Regulation, Neoplastic
Humans
In Vitro Techniques
Insulin-Like Growth Factor II - genetics
Kidneys
Medical sciences
Molecular Sequence Data
Nephrology. Urinary tract diseases
Promoter Regions, Genetic
RNA, Messenger - genetics
Transcription Factors - physiology
Transcriptional Activation
Tumor Cells, Cultured
Tumors of the urinary system
Wilms Tumor - metabolism
WT1 Proteins
Zinc Fingers
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:The Wilms' tumor suppressor gene WT1 encodes a zinc finger transcription factor, whose expression inhibits the growth of the RM1 Wilms' tumor cell line. Transient transfection of WT1 constructs into 3T3 or 293 cells results in transcriptional repression of a number of cotransfected promoters containing the early growth response gene 1 consensus sequence. We now show that WT1 has properties of a transcriptional activator in RM1 cells, an effect that may be associated with the presence of a mutated p53 gene in these cells. Stable transfection of wild-type WT1 into RM1 cells results in induction of endogenous insulin-like growth factor 2 (IGF2) but not of other previously postulated WT1-target genes. The induction of IGF2 is dramatically enhanced by WT1 mutants encoding an altered transactivation domain. We conclude that IGF2 is a potentially physiological target gene for WT1 and that its induction may contribute to the growth-stimulating effects of WT1 variants.
ISSN:0008-5472
1538-7445