Induction of p21 by the Wilms' tumor suppressor gene WT1

WT1 encodes a zinc finger transcription factor that is expressed in the developing kidney and the inactivation of which leads to Wilms' tumor, a pediatric kidney cancer. We have recently shown that inducible expression of WT1 in osteosarcoma cells triggers programmed cell death, an effect that...

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Bibliographic Details
Published in:Cancer research (Chicago, Ill.) Ill.), 1997-04, Vol.57 (8), p.1429-1434
Main Authors: ENGLERT, C, MAHESWARAN, S, GARVIN, A. J, KREIDBERG, J, HABER, D. A
Format: Article
Language:English
Subjects:
Anti-Bacterial Agents - pharmacology
Biological and medical sciences
Blotting, Western
Cyclin-Dependent Kinase Inhibitor p21
Cyclins - metabolism
DNA-Binding Proteins - genetics
DNA-Binding Proteins - physiology
Flow Cytometry - methods
G1 Phase - drug effects
G1 Phase - genetics
Genes, p53 - genetics
Genes, p53 - physiology
Genes, Wilms Tumor - genetics
Genes, Wilms Tumor - physiology
Humans
Kidney - embryology
Kidney - metabolism
Kidneys
Medical sciences
Mutation
Neoplasm Proteins - metabolism
Nephrology. Urinary tract diseases
Osteosarcoma - genetics
Osteosarcoma - metabolism
RNA, Messenger - metabolism
Tetracycline - pharmacology
Transcription Factors - genetics
Transcription Factors - physiology
Transfection
Tumor Cells, Cultured
Tumor Suppressor Protein p53 - genetics
Tumor Suppressor Protein p53 - physiology
Tumors of the urinary system
WT1 Proteins
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Summary:WT1 encodes a zinc finger transcription factor that is expressed in the developing kidney and the inactivation of which leads to Wilms' tumor, a pediatric kidney cancer. We have recently shown that inducible expression of WT1 in osteosarcoma cells triggers programmed cell death, an effect that is associated with transcriptional repression of the endogenous epidermal growth factor receptor. We now show that WT1-mediated apoptosis is preceded by induction of the cyclin-dependent kinase inhibitor p21, associated with G1 phase arrest. This effect is only demonstrated by WT1 isoforms with an intact DNA binding domain, and it is associated with increased expression of endogenous p21 mRNA. WT1-mediated induction of p21 is independent of p53, another tumor suppressor gene known to regulate p21 expression. In the kidney, p21 is expressed in differentiating glomerular podocytes along with WT1. We conclude that induction of p21 expression may contribute to WT1-dependent differentiation pathways in the kidney and potentially to the function of WT1 as a tumor suppressor gene.
ISSN:0008-5472
1538-7445