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Repression of the Insulin-Like Growth Factor II Gene by the Wilms Tumor Suppressor WT1
Abstract
The Wilms tumor suppressor gene wt1 encodes a zinc finger DNA binding protein, WT1, that functions as a transcriptional repressor. The fetal mitogen insulin-like growth factor II (IGF-II) is overexpressed in Wilms tumors and may have autocrine effects in tumor progression. The major fetal IGF-II promoter was defined in transient transfection assays as a region spanning from nucleotides -295 to +135, relative to the transcription start site. WT1 bound to multiple sites in this region and functioned as a potent repressor of IGF-II transcription in vivo. Maximal repression was dependent on the presence of WT1 binding sites on each side of the transcriptional initiation site. These findings provide a molecular basis for overexpression of IGF-II in Wilms tumors and suggest that WT1 negatively regulates blastemal cell proliferation by limiting the production of a fetal growth factor in the developing vertebrate kidney.
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Cited by
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Nelen, M. R., Padberg, G. W., Peeters, E. A. J., Lin, A. Y., Helm, B. V. D., Frants, R. R., Goulon, V., Goldstein, A. M., Reen, M. M. M. V., Eastern, D. F., et al. (1996) · Nature Genetics · doi:10.1038/ng0596-114 · Cited by 668
WT1 proteins: functions in growth and differentiation
Scharnhorst, V., van der Eb, A. J., & Jochemsen, A. G. (2001) · Gene · doi:10.1016/s0378-1119(01)00593-5 · Cited by 353
Insulin-like Growth Factors and Cancer
LeRoith, D., Baserga, R., Helman, L., & Roberts Jr., C. T. (1995) · Annals of Internal Medicine · doi:10.7326/0003-4819-122-1-199501010-00009 · Cited by 317
Non-Islet Cell Tumour-Induced Hypoglycaemia: A Review of the Literature Including Two New Cases
de Groot, J. W. B., Rikhof, B., van Doorn, J., Bilo, H. J. G., Alleman, M. A., Honkoop, A. H., & van der Graaf, W. T. A. (2007) · Endocrine Related Cancer · doi:10.1677/erc-07-0161 · Cited by 222
Metadata
- Authors
- Drummond, L. A., Madden, S. L., Rohwer-Nutter, P., Bell, G. I., Sukhatme, V. P., & Rauscher, F. J.
- Venue
- Science
- Published
- 1992-07-31
- Volume
- 257
- Issue
- 5070
- Pages
- 674-678
- ISSN
- 0036-8075 (ISSN-L)
- 1095-9203
- OpenAlex
- W2010791130
- Cited by
- 525
- References
- 0
- FWCI
- 17.56
- Type
- journal article
- Language
- en
- Open access
- closed
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- Drummond, L. A., Madden, S. L., Rohwer-Nutter, P., Bell, G. I., Sukhatme, V. P., & Rauscher, F. J. (1992). Repression of the Insulin-Like Growth Factor II Gene by the Wilms Tumor Suppressor WT1. Science. https://doi.org/10.1126/science.1323141
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Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).
Semantic Scholar’s data is described in: Kinney, R., et al. (2023). The Semantic Scholar Open Data Platform. arXiv:2301.10140.
