![[Feedback]](/icons/banner/feedbackACT.gif){kind=icon}
![[For Subscribers]](/icons/banner/subscriberACT.gif){kind=icon}
![[Archive]](/icons/banner/archiveACT.gif){kind=icon}
![[Search]](/icons/banner/searchACT.gif){kind=icon}
![[Contents]](/icons/banner/tocACT.gif){kind=icon}
|
|
|
|
|
||
Research Papers
Center for Cancer Research, Massachusetts Institute of Technology, Cambridge 02139.
Abstract
The Wilms' tumor gene WT1 is a recessive oncogene that encodes a putative transcription factor implicated in nephrogenesis during kidney development. In this report we analyze expression of WT1 in the murine urogenital system. WT1 is expressed in non-germ-cell components of the testis and ovaries in both young and adult mice. In situ mRNA hybridization studies demonstrate that WT1 is expressed in the granulosa and epithelial cells of ovaries, the Sertoli cells of the testis, and in the uterine wall. In addition to the 3.1-kb WT1 transcript detected by Northern blotting of RNA from kidney, uterus, and gonads, there is an approximately 2.5-kb WT1-related mRNA species in testis. The levels of WT1 mRNA in the gonads are among the highest observed, surpassing amounts detected in the embryonic kidney. During development, these levels are differentially regulated, depending on the sexual differentiation of the gonad. Expression of WT1 mRNA in the female reproductive system does not fluctuate significantly from days 4 to 40 postpartum. In contrast, WT1 mRNA levels in the tesis increase steadily after birth, reaching their highest expression levels at day 8 postpartum and decreasing slightly as the animal matures. Expression of WT1 in the gonads is detectable as early as 12.5 days postcoitum (p.c.). As an initial step toward exploring the tissue-specific expression of WT1, DNA elements upstream of WT1 were cloned and sequenced. Three putative transcription initiation sites, utilized in testis, ovaries, and uterus, were mapped by S1 nuclease protection assays. The sequences surrounding these sites have a high G + C content, and typical upstream CCAAT and TATAA boxes are not present. These studies allowed us to identify the translation initiation site for WT1 protein synthesis. We have also used an epitope-tagging protocol to demonstrate that WT1 is a nuclear protein, consistent with its role as a transcription factor. Our results demonstrate regulation of WT1 expression during development of the gonads, implicate WT1 in genitourinary development, and provide a molecular framework toward understanding genitourinary defects observed among hereditary cases of Wilms' tumor.
CiteULike 
Connotea 
Del.icio.us 
Digg 
Reddit 
Technorati What's this?
This article has been cited by other articles:
|
|
 |
|
  S. E. Quaggin and J. A. Kreidberg Development of the renal glomerulus: good neighbors and good fences Development, February 15, 2008; 135(4): 609 - 620. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. R. Dallosso, A. L. Hancock, S. Malik, A. Salpekar, L. King-Underwood, K. Pritchard-Jones, J. Peters, K. Moorwood, A. Ward, K. T.A. Malik, et al. Alternately spliced WT1 antisense transcripts interact with WT1 sense RNA and show epigenetic and splicing defects in cancer RNA, December 1, 2007; 13(12): 2287 - 2299. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. Klattig, R. Sierig, D. Kruspe, B. Besenbeck, and C. Englert Wilms' Tumor Protein Wt1 Is an Activator of the Anti-Mullerian Hormone Receptor Gene Amhr2 Mol. Cell. Biol., June 15, 2007; 27(12): 4355 - 4364. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. Dame, K. M. Kirschner, K. V. Bartz, T. Wallach, C. S. Hussels, and H. Scholz Wilms tumor suppressor, Wt1, is a transcriptional activator of the erythropoietin gene Blood, June 1, 2006; 107(11): 4282 - 4290. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. K. Rao, J. Pham, J. S. Imam, J. A. MacLean, D. Murali, Y. Furuta, A. P. Sinha-Hikim, and M. F. Wilkinson Tissue-specific RNAi reveals that WT1 expression in nurse cells controls germ cell survival and spermatogenesis Genes & Dev., January 15, 2006; 20(2): 147 - 152. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
X. Gao, X. Chen, M. Taglienti, B. Rumballe, M. H. Little, and J. A. Kreidberg Angioblast-mesenchyme induction of early kidney development is mediated by Wt1 and Vegfa Development, December 15, 2005; 132(24): 5437 - 5449. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
N. Wagner, K.-D. Wagner, H. Theres, C. Englert, A. Schedl, and H. Scholz Coronary vessel development requires activation of the TrkB neurotrophin receptor by the Wilms' tumor transcription factor Wt1 Genes & Dev., November 1, 2005; 19(21): 2631 - 2642. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
G. J. Bouma, K. H. Albrecht, L. L. Washburn, A. K. Recknagel, G. A. Churchill, and E. M. Eicher Gonadal sex reversal in mutant Dax1 XY mice: a failure to upregulate Sox9 in pre-Sertoli cells Development, July 1, 2005; 132(13): 3045 - 3054. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
V. Tohonen, J. Frygelius, M. Mohammadieh, U. Kvist, L. J. Pelliniemi, K. O'Brien, K. Nordqvist, and A. Wedell Normal Sexual Development and Fertility in testatin Knockout Mice Mol. Cell. Biol., June 15, 2005; 25(12): 4892 - 4902. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K. L. Britt, P. K. Saunders, S. J. McPherson, M. L. Misso, E. R. Simpson, and J. K. Findlay Estrogen Actions on Follicle Formation and Early Follicle Development Biol Reprod, November 1, 2004; 71(5): 1712 - 1723. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K. L. Britt, P. G. Stanton, M. Misso, E. R. Simpson, and J. K. Findlay The Effects of Estrogen on the Expression of Genes Underlying the Differentiation of Somatic Cells in the Murine Gonad Endocrinology, August 1, 2004; 145(8): 3950 - 3960. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Y. Hong, T. Liu, H. Zhao, H. Xu, W. Wang, R. Liu, T. Chen, J. Deng, and J. Gui Establishment of a normal medakafish spermatogonial cell line capable of sperm production in vitro PNAS, May 25, 2004; 101(21): 8011 - 8016. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. T. Discenza and J. Pelletier Insights into the physiological role of WT1 from studies of genetically modified mice Physiol Genomics, February 13, 2004; 16(3): 287 - 300. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. Ribes, E. Fischer, A. Calmont, and J. Rossert Transcriptional Control of Epithelial Differentiation during Kidney Development J. Am. Soc. Nephrol., June 1, 2003; 14(90001): S9 - 15. [Full Text] [PDF]
|
|
|
|
|
|
C. G. Miles, J. Slight, L. Spraggon, M. O'Sullivan, C. Patek, and N. D. Hastie Mice Lacking the 68-Amino-Acid, Mammal-Specific N-Terminal Extension of WT1 Develop Normally and Are Fertile Mol. Cell. Biol., April 1, 2003; 23(7): 2608 - 2613. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
N. Sakai Transmeiotic differentiation of zebrafish germ cells into functional sperm in culture Development, March 9, 2003; 129(14): 3359 - 3365. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. A. Kreidberg Podocyte Differentiation and Glomerulogenesis J. Am. Soc. Nephrol., March 1, 2003; 14(3): 806 - 814. [Full Text] [PDF]
|
|
|
|
|
|
K. A. Logan, K. P. McNatty, and J. L. Juengel Expression of Wilms' Tumor Gene and Protein Localization During Ovarian Formation and Follicular Development in Sheep Biol Reprod, February 1, 2003; 68(2): 635 - 643. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
I. Bellantuono, L. Gao, S. Parry, S. Marley, F. Dazzi, J. Apperley, J. M. Goldman, and H. J. Stauss Two distinct HLA-A0201-presented epitopes of the Wilms tumor antigen 1 can function as targets for leukemia-reactive CTL Blood, November 15, 2002; 100(10): 3835 - 3837. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 B. Gurates, S. Sebastian, S. Yang, J. Zhou, M. Tamura, Z. Fang, T. Suzuki, H. Sasano, and S. E. Bulun WT1 and DAX-1 Inhibit Aromatase P450 Expression in Human Endometrial and Endometriotic Stromal Cells J. Clin. Endocrinol. Metab., September 1, 2002; 87(9): 4369 - 4377. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Makita, A. Hiraki, T. Azuma, A. Tsuboi, Y. Oka, H. Sugiyama, S. Fujita, M. Tanimoto, M. Harada, and M. Yasukawa Antilung Cancer Effect of WT1-specific Cytotoxic T Lymphocytes Clin. Cancer Res., August 1, 2002; 8(8): 2626 - 2631. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. A. Natoli, A. McDonald, J. A. Alberta, M. E. Taglienti, D. E. Housman, and J. A. Kreidberg A Mammal-Specific Exon of WT1 Is Not Required for Development or Fertility Mol. Cell. Biol., June 15, 2002; 22(12): 4433 - 4438. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. G. Tevosian, K. H. Albrecht, J. D. Crispino, Y. Fujiwara, E. M. Eicher, and S. H. Orkin Gonadal differentiation, sex determination and normal Sry expression in mice require direct interaction between transcription partners GATA4 and FOG2 Development, January 10, 2002; 129(19): 4627 - 4634. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P. M. Timmons, P. W. J. Rigby, and F. Poirier The murine seminiferous epithelial cycle is pre-figured in the Sertoli cells of the embryonic testis Development, January 2, 2002; 129(3): 635 - 647. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Makrigiannakis, G. Coukos, A. Mantani, P. Prokopakis, G. Trew, R. Margara, R. Winston, and J. White Expression of Wilms' Tumor Suppressor Gene (WT1) in Human Endometrium: Regulation through Decidual Differentiation J. Clin. Endocrinol. Metab., December 1, 2001; 86(12): 5964 - 5972. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Dutertre, L. Gouedard, F. Xavier, W.-Q. Long, N. di Clemente, J.-Y. Picard, and R. Rey Ovarian Granulosa Cell Tumors Express a Functional Membrane Receptor for Anti-Mullerian Hormone in Transgenic Mice Endocrinology, September 1, 2001; 142(9): 4040 - 4046. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
F. C. Serluca and M. C. Fishman Pre-pattern in the pronephric kidney field of zebrafish Development, June 15, 2001; 128(12): 2233 - 2241. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 X. Meng, D. G. de Rooij, K. Westerdahl, M. Saarma, and H. Sariola Promotion of Seminomatous Tumors by Targeted Overexpression of Glial Cell Line-derived Neurotrophic Factor in Mouse Testis Cancer Res., April 1, 2001; 61(8): 3267 - 3271. [Abstract] [Full Text]
|
|
|
|
 |
|
 L. Gnessi, S. Basciani, S. Mariani, M. Arizzi, G. Spera, C. Wang, C. Bondjers, L. Karlsson, and C. Betsholtz Leydig Cell Loss and Spermatogenic Arrest in Platelet-derived Growth Factor (PDGF)-A-deficient Mice J. Cell Biol., May 29, 2000; 149(5): 1019 - 1026. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Hosono, I. Gross, M. A. English, K. M. Hajra, E. R. Fearon, and J. D. Licht E-cadherin Is a WT1 Target Gene J. Biol. Chem., April 6, 2000; 275(15): 10943 - 10953. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. A.F. Daggett, D. A. Rice, and L. L. Heckert Expression of Steroidogenic Factor 1 in the Testis Requires an E Box and CCAAT Box in its Promoter Proximal Region Biol Reprod, March 1, 2000; 62(3): 670 - 679. [Abstract] [Full Text]
|
|
|
|
|
|
H. Ohminami, M. Yasukawa, and S. Fujita HLA class I-restricted lysis of leukemia cells by a CD8+ cytotoxic T-lymphocyte clone specific for WT1 peptide Blood, January 1, 2000; 95(1): 286 - 293. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. J. Tremblay and R. S. Viger Transcription Factor GATA-4 Enhances Mullerian Inhibiting Substance Gene Transcription through a Direct Interaction with the Nuclear Receptor SF-1 Mol. Endocrinol., August 1, 1999; 13(8): 1388 - 1401. [Abstract] [Full Text]
|
|
|
|
|
|
A. Swain and R. Lovell-Badge Mammalian sex determination: a molecular drama Genes & Dev., April 1, 1999; 13(7): 755 - 767. [Full Text]
|
|
|
|
|
|
J. Kim, D. Prawitt, N. Bardeesy, E. Torban, C. Vicaner, P. Goodyer, B. Zabel, and J. Pelletier The Wilms' Tumor Suppressor Gene (wt1) Product Regulates Dax-1 Gene Expression during Gonadal Differentiation Mol. Cell. Biol., March 1, 1999; 19(3): 2289 - 2299. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S.-Y. Chun, E. A. McGee, S. Y. Hsu, S. Minami, P. S. LaPolt, H. H.-C. Yao, J. M. Bahr, A. Gougeon, D. W. Schomberg, and A. J.W. Hsueh Restricted Expression of WT1 Messenger Ribonucleic Acid in Immature Ovarian Follicles: Uniformity in Mammalian and Avian Species and Maintenance during Reproductive Senescence Biol Reprod, February 1, 1999; 60(2): 365 - 373. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 U Muller and A. Brandli Cell adhesion molecules and extracellular-matrix constituents in kidney development and disease J. Cell Sci., January 11, 1999; 112(22): 3855 - 3867. [Abstract] [PDF]
|
|
|
|
|
|
A. Moore, L McInnes, J Kreidberg, N. Hastie, and A Schedl YAC complementation shows a requirement for Wt1 in the development of epicardium, adrenal gland and throughout nephrogenesis Development, January 5, 1999; 126(9): 1845 - 1857. [Abstract] [PDF]
|
|
|
|
|
|
L.-S. Guan, M. Rauchman, and Z.-Y. Wang Induction of Rb-associated Protein (RbAp46) by Wilms' Tumor Suppressor WT1 Mediates Growth Inhibition J. Biol. Chem., October 16, 1998; 273(42): 27047 - 27050. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Feingold, M. Zilberstein, R. K. Srivastava, M. M. Seibel, S. Bar-Ami, and E. Hambartsoumian Expression of Wilms' Tumor Suppressor Gene (WT1) in Term Human Trophoblast: Regulation by Cyclic Adenosine 3',5'-Monophosphate J. Clin. Endocrinol. Metab., July 1, 1998; 83(7): 2503 - 2508. [Abstract] [Full Text]
|
|
|
|
|
|
R. Viger, C Mertineit, J. Trasler, and M Nemer Transcription factor GATA-4 is expressed in a sexually dimorphic pattern during mouse gonadal development and is a potent activator of the Mullerian inhibiting substance promoter Development, January 7, 1998; 125(14): 2665 - 2675. [Abstract] [PDF]
|
|
|
|
|
|
G. C. Fraizer, R. Shimamura, X. Zhang, and G. F. Saunders PAX 8 Regulates Human WT1 Transcription through a Novel DNA Binding Site J. Biol. Chem., December 5, 1997; 272(49): 30678 - 30687. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
X. Zhang, G. Xing, G. C. Fraizer, and G. F. Saunders Transactivation of an Intronic Hematopoietic-specific Enhancer of the Human Wilms' Tumor 1 Gene by GATA-1 and c-Myb J. Biol. Chem., November 14, 1997; 272(46): 29272 - 29280. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. Amsterdam and N. Selvaraj Control of Differentiation, Transformation, and Apoptosis in Granulosa Cells by Oncogenes, Oncoviruses, and Tumor Suppressor Genes Endocr. Rev., August 1, 1997; 18(4): 435 - 461. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
G. B. Silberstein, K. Van Horn, P. Strickland, C. T. Roberts Jr., and C. W. Daniel Altered expression of the WT1 Wilms tumor suppressor gene in human breast cancer PNAS, July 22, 1997; 94(15): 8132 - 8137. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. T. Cohen, S. A. Bossone, G. Zhu, G. A. McDonald, and V. P. Sukhatme Sp1 Is a Critical Regulator of the Wilms' tumor-1 Gene J. Biol. Chem., January 31, 1997; 272(5): 2901 - 2913. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
N Miyamoto, M Yoshida, S Kuratani, I Matsuo, and S Aizawa Defects of urogenital development in mice lacking Emx2 Development, January 5, 1997; 124(9): 1653 - 1664. [Abstract] [PDF]
|
|
|
|
|
|
I. Karavanova, L. Dove, J. Resau, and A. Perantoni Conditioned medium from a rat ureteric bud cell line in combination with bFGF induces complete differentiation of isolated metanephric mesenchyme Development, January 12, 1996; 122(12): 4159 - 4167. [Abstract] [PDF]
|
|
|
|
|
|
A Schuchardt, V D'Agati, V Pachnis, and F Costantini Renal agenesis and hypodysplasia in ret-k- mutant mice result from defects in ureteric bud development Development, January 6, 1996; 122(6): 1919 - 1929. [Abstract] [PDF]
|
|
|
|
|
|
B Capel, J. Hawkins, E Hirst, D Kioussis, and R Lovell-Badge Establishment and characterization of conditionally immortalized cells from the mouse urogenital ridge J. Cell Sci., January 5, 1996; 109(5): 899 - 909. [Abstract] [PDF]
|
|
|
|
 |
|
 M. J. Coppes, D. A. Haber, and P. E. Grundy Genetic Events in the Development of Wilms' Tumor N. Engl. J. Med., September 1, 1994; 331(9): 586 - 590. [Full Text]
|
|
|
|
|
|
P M Sharma, M Bowman, S L Madden, F J Rauscher, and S Sukumar RNA editing in the Wilms' tumor susceptibility gene, WT1. Genes & Dev., March 15, 1994; 8(6): 720 - 731. [Abstract] [PDF]
|
|
|
|
|
|
S. Mundlos, J. Pelletier, A. Darveau, M. Bachmann, A. Winterpacht, and B. Zabel Nuclear localization of the protein encoded by the Wilms' tumor gene WT1 in embryonic and adult tissues Development, December 1, 1993; 119(4): 1329 - 1341. [Abstract] [PDF]
|
|
|
|
 |
|
 I. Drummond, S. Madden, P Rohwer-Nutter, G. Bell, V. Sukhatme, and F. Rauscher 3rd Repression of the insulin-like growth factor II gene by the Wilms tumor suppressor WT1 Science, July 31, 1992; 257(5070): 674 - 678. [Abstract] [PDF]
|
|
|
|
|
|
R. Weinberg Tumor suppressor genes Science, November 22, 1991; 254(5035): 1138 - 1146. [Abstract] [PDF]
|
|
|
|
|
|
W. Wang, S. B. Lee, R. Palmer, L. W. Ellisen, and D. A. Haber A Functional Interaction with CBP Contributes to Transcriptional Activation by the Wilms Tumor Suppressor WT1 J. Biol. Chem., May 11, 2001; 276(20): 16810 - 16816. [Abstract] [Full Text] [PDF]
|
|
