WT1 suppresses synthesis of the epidermal growth factor receptor and induces apoptosis (original) (raw)

Abstract

The Wilms tumor suppressor gene WT1 encodes a developmentally regulated transcription factor that is mutated in a subset of embryonal tumors. To test its functional properties, we developed osteosarcoma cell lines expressing WT1 under an inducible tetracycline-regulated promoter. Induction of WT1 resulted in programmed cell death. This effect, which was differentially mediated by the alternative splicing variants of WT1, was independent of p53. WT1-mediated apoptosis was associated with reduced synthesis of the epidermal growth factor receptor (EGFR), but not of other postulated WT1-target genes, and it was abrogated by constitutive expression of EGFR. WT1 repressed transcription from the EGFR promoter, binding to two TC-rich repeat sequences. In the developing kidney, EGFR expression in renal precursor cells declined with the onset of WT1 expression. Repression of EGFR and induction of apoptosis by mechanism that may contribute to its critical role in normal kidney development and to the immortalization of tumor cells with inactivated WT1 alleles.

4662

Images in this article

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Armstrong J. F., Pritchard-Jones K., Bickmore W. A., Hastie N. D., Bard J. B. The expression of the Wilms' tumour gene, WT1, in the developing mammalian embryo. Mech Dev. 1993 Jan;40(1-2):85–97. doi: 10.1016/0925-4773(93)90090-k. [DOI] [PubMed] [Google Scholar]
  2. Auffray C., Rougeon F. Purification of mouse immunoglobulin heavy-chain messenger RNAs from total myeloma tumor RNA. Eur J Biochem. 1980 Jun;107(2):303–314. doi: 10.1111/j.1432-1033.1980.tb06030.x. [DOI] [PubMed] [Google Scholar]
  3. Baker S. J., Markowitz S., Fearon E. R., Willson J. K., Vogelstein B. Suppression of human colorectal carcinoma cell growth by wild-type p53. Science. 1990 Aug 24;249(4971):912–915. doi: 10.1126/science.2144057. [DOI] [PubMed] [Google Scholar]
  4. Baserga R. Oncogenes and the strategy of growth factors. Cell. 1994 Dec 16;79(6):927–930. doi: 10.1016/0092-8674(94)90023-x. [DOI] [PubMed] [Google Scholar]
  5. Beckwith J. B., Kiviat N. B., Bonadio J. F. Nephrogenic rests, nephroblastomatosis, and the pathogenesis of Wilms' tumor. Pediatr Pathol. 1990;10(1-2):1–36. doi: 10.3109/15513819009067094. [DOI] [PubMed] [Google Scholar]
  6. Bickmore W. A., Oghene K., Little M. H., Seawright A., van Heyningen V., Hastie N. D. Modulation of DNA binding specificity by alternative splicing of the Wilms tumor wt1 gene transcript. Science. 1992 Jul 10;257(5067):235–237. doi: 10.1126/science.1321494. [DOI] [PubMed] [Google Scholar]
  7. Bove K. E., McAdams A. J. The nephroblastomatosis complex and its relationship to Wilms' tumor: a clinicopathologic treatise. Perspect Pediatr Pathol. 1976;3:185–223. [PubMed] [Google Scholar]
  8. Buckler A. J., Pelletier J., Haber D. A., Glaser T., Housman D. E. Isolation, characterization, and expression of the murine Wilms' tumor gene (WT1) during kidney development. Mol Cell Biol. 1991 Mar;11(3):1707–1712. doi: 10.1128/mcb.11.3.1707. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Caelles C., Helmberg A., Karin M. p53-dependent apoptosis in the absence of transcriptional activation of p53-target genes. Nature. 1994 Jul 21;370(6486):220–223. doi: 10.1038/370220a0. [DOI] [PubMed] [Google Scholar]
  10. Call K. M., Glaser T., Ito C. Y., Buckler A. J., Pelletier J., Haber D. A., Rose E. A., Kral A., Yeger H., Lewis W. H. Isolation and characterization of a zinc finger polypeptide gene at the human chromosome 11 Wilms' tumor locus. Cell. 1990 Feb 9;60(3):509–520. doi: 10.1016/0092-8674(90)90601-a. [DOI] [PubMed] [Google Scholar]
  11. Coles H. S., Burne J. F., Raff M. C. Large-scale normal cell death in the developing rat kidney and its reduction by epidermal growth factor. Development. 1993 Jul;118(3):777–784. doi: 10.1242/dev.118.3.777. [DOI] [PubMed] [Google Scholar]
  12. Dey B. R., Sukhatme V. P., Roberts A. B., Sporn M. B., Rauscher F. J., 3rd, Kim S. J. Repression of the transforming growth factor-beta 1 gene by the Wilms' tumor suppressor WT1 gene product. Mol Endocrinol. 1994 May;8(5):595–602. doi: 10.1210/mend.8.5.8058069. [DOI] [PubMed] [Google Scholar]
  13. Di Fiore P. P., Pierce J. H., Fleming T. P., Hazan R., Ullrich A., King C. R., Schlessinger J., Aaronson S. A. Overexpression of the human EGF receptor confers an EGF-dependent transformed phenotype to NIH 3T3 cells. Cell. 1987 Dec 24;51(6):1063–1070. doi: 10.1016/0092-8674(87)90592-7. [DOI] [PubMed] [Google Scholar]
  14. Diller L., Kassel J., Nelson C. E., Gryka M. A., Litwak G., Gebhardt M., Bressac B., Ozturk M., Baker S. J., Vogelstein B. p53 functions as a cell cycle control protein in osteosarcomas. Mol Cell Biol. 1990 Nov;10(11):5772–5781. doi: 10.1128/mcb.10.11.5772. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Drummond I. A., Madden S. L., Rohwer-Nutter P., Bell G. I., Sukhatme V. P., Rauscher F. J., 3rd Repression of the insulin-like growth factor II gene by the Wilms tumor suppressor WT1. Science. 1992 Jul 31;257(5070):674–678. doi: 10.1126/science.1323141. [DOI] [PubMed] [Google Scholar]
  16. Drummond I. A., Rupprecht H. D., Rohwer-Nutter P., Lopez-Guisa J. M., Madden S. L., Rauscher F. J., 3rd, Sukhatme V. P. DNA recognition by splicing variants of the Wilms' tumor suppressor, WT1. Mol Cell Biol. 1994 Jun;14(6):3800–3809. doi: 10.1128/mcb.14.6.3800. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Evan G. I., Wyllie A. H., Gilbert C. S., Littlewood T. D., Land H., Brooks M., Waters C. M., Penn L. Z., Hancock D. C. Induction of apoptosis in fibroblasts by c-myc protein. Cell. 1992 Apr 3;69(1):119–128. doi: 10.1016/0092-8674(92)90123-t. [DOI] [PubMed] [Google Scholar]
  18. Fairbairn L. J., Cowling G. J., Reipert B. M., Dexter T. M. Suppression of apoptosis allows differentiation and development of a multipotent hemopoietic cell line in the absence of added growth factors. Cell. 1993 Sep 10;74(5):823–832. doi: 10.1016/0092-8674(93)90462-y. [DOI] [PubMed] [Google Scholar]
  19. Fisher D. A., Salido E. C., Barajas L. Epidermal growth factor and the kidney. Annu Rev Physiol. 1989;51:67–80. doi: 10.1146/annurev.ph.51.030189.000435. [DOI] [PubMed] [Google Scholar]
  20. Fried M., Crothers D. M. Equilibria and kinetics of lac repressor-operator interactions by polyacrylamide gel electrophoresis. Nucleic Acids Res. 1981 Dec 11;9(23):6505–6525. doi: 10.1093/nar/9.23.6505. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Gashler A. L., Bonthron D. T., Madden S. L., Rauscher F. J., 3rd, Collins T., Sukhatme V. P. Human platelet-derived growth factor A chain is transcriptionally repressed by the Wilms tumor suppressor WT1. Proc Natl Acad Sci U S A. 1992 Nov 15;89(22):10984–10988. doi: 10.1073/pnas.89.22.10984. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Gessler M., Poustka A., Cavenee W., Neve R. L., Orkin S. H., Bruns G. A. Homozygous deletion in Wilms tumours of a zinc-finger gene identified by chromosome jumping. Nature. 1990 Feb 22;343(6260):774–778. doi: 10.1038/343774a0. [DOI] [PubMed] [Google Scholar]
  23. Glaser T., Lane J., Housman D. A mouse model of the aniridia-Wilms tumor deletion syndrome. Science. 1990 Nov 9;250(4982):823–827. doi: 10.1126/science.2173141. [DOI] [PubMed] [Google Scholar]
  24. Gossen M., Bujard H. Tight control of gene expression in mammalian cells by tetracycline-responsive promoters. Proc Natl Acad Sci U S A. 1992 Jun 15;89(12):5547–5551. doi: 10.1073/pnas.89.12.5547. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Haber D. A., Buckler A. J., Glaser T., Call K. M., Pelletier J., Sohn R. L., Douglass E. C., Housman D. E. An internal deletion within an 11p13 zinc finger gene contributes to the development of Wilms' tumor. Cell. 1990 Jun 29;61(7):1257–1269. doi: 10.1016/0092-8674(90)90690-g. [DOI] [PubMed] [Google Scholar]
  26. Haber D. A., Housman D. E. The genetics of Wilms' tumor. Adv Cancer Res. 1992;59:41–68. doi: 10.1016/s0065-230x(08)60302-4. [DOI] [PubMed] [Google Scholar]
  27. Haber D. A., Park S., Maheswaran S., Englert C., Re G. G., Hazen-Martin D. J., Sens D. A., Garvin A. J. WT1-mediated growth suppression of Wilms tumor cells expressing a WT1 splicing variant. Science. 1993 Dec 24;262(5142):2057–2059. doi: 10.1126/science.8266105. [DOI] [PubMed] [Google Scholar]
  28. Haber D. A., Sohn R. L., Buckler A. J., Pelletier J., Call K. M., Housman D. E. Alternative splicing and genomic structure of the Wilms tumor gene WT1. Proc Natl Acad Sci U S A. 1991 Nov 1;88(21):9618–9622. doi: 10.1073/pnas.88.21.9618. [DOI] [PMC free article] [PubMed] [Google Scholar]
  29. Haber D. A., Timmers H. T., Pelletier J., Sharp P. A., Housman D. E. A dominant mutation in the Wilms tumor gene WT1 cooperates with the viral oncogene E1A in transformation of primary kidney cells. Proc Natl Acad Sci U S A. 1992 Jul 1;89(13):6010–6014. doi: 10.1073/pnas.89.13.6010. [DOI] [PMC free article] [PubMed] [Google Scholar]
  30. Harrington M. A., Konicek B., Song A., Xia X. L., Fredericks W. J., Rauscher F. J., 3rd Inhibition of colony-stimulating factor-1 promoter activity by the product of the Wilms' tumor locus. J Biol Chem. 1993 Oct 5;268(28):21271–21275. [PubMed] [Google Scholar]
  31. Hentschel C. C. Homocopolymer sequences in the spacer of a sea urchin histone gene repeat are sensitive to S1 nuclease. Nature. 1982 Feb 25;295(5851):714–716. doi: 10.1038/295714a0. [DOI] [PubMed] [Google Scholar]
  32. Htun H., Lund E., Dahlberg J. E. Human U1 RNA genes contain an unusually sensitive nuclease S1 cleavage site within the conserved 3' flanking region. Proc Natl Acad Sci U S A. 1984 Dec;81(23):7288–7292. doi: 10.1073/pnas.81.23.7288. [DOI] [PMC free article] [PubMed] [Google Scholar]
  33. Jacobson M. D., Burne J. F., King M. P., Miyashita T., Reed J. C., Raff M. C. Bcl-2 blocks apoptosis in cells lacking mitochondrial DNA. Nature. 1993 Jan 28;361(6410):365–369. doi: 10.1038/361365a0. [DOI] [PubMed] [Google Scholar]
  34. Johnson A. C., Ishii S., Jinno Y., Pastan I., Merlino G. T. Epidermal growth factor receptor gene promoter. Deletion analysis and identification of nuclear protein binding sites. J Biol Chem. 1988 Apr 25;263(12):5693–5699. [PubMed] [Google Scholar]
  35. Johnson A. C., Jinno Y., Merlino G. T. Modulation of epidermal growth factor receptor proto-oncogene transcription by a promoter site sensitive to S1 nuclease. Mol Cell Biol. 1988 Oct;8(10):4174–4184. doi: 10.1128/mcb.8.10.4174. [DOI] [PMC free article] [PubMed] [Google Scholar]
  36. Koseki C., Herzlinger D., al-Awqati Q. Apoptosis in metanephric development. J Cell Biol. 1992 Dec;119(5):1327–1333. doi: 10.1083/jcb.119.5.1327. [DOI] [PMC free article] [PubMed] [Google Scholar]
  37. Kreidberg J. A., Sariola H., Loring J. M., Maeda M., Pelletier J., Housman D., Jaenisch R. WT-1 is required for early kidney development. Cell. 1993 Aug 27;74(4):679–691. doi: 10.1016/0092-8674(93)90515-r. [DOI] [PubMed] [Google Scholar]
  38. Ladanyi M., Gerald W. Fusion of the EWS and WT1 genes in the desmoplastic small round cell tumor. Cancer Res. 1994 Jun 1;54(11):2837–2840. [PubMed] [Google Scholar]
  39. Larsson S. H., Charlieu J. P., Miyagawa K., Engelkamp D., Rassoulzadegan M., Ross A., Cuzin F., van Heyningen V., Hastie N. D. Subnuclear localization of WT1 in splicing or transcription factor domains is regulated by alternative splicing. Cell. 1995 May 5;81(3):391–401. doi: 10.1016/0092-8674(95)90392-5. [DOI] [PubMed] [Google Scholar]
  40. Luckow B., Schütz G. CAT constructions with multiple unique restriction sites for the functional analysis of eukaryotic promoters and regulatory elements. Nucleic Acids Res. 1987 Jul 10;15(13):5490–5490. doi: 10.1093/nar/15.13.5490. [DOI] [PMC free article] [PubMed] [Google Scholar]
  41. Mace H. A., Pelham H. R., Travers A. A. Association of an S1 nuclease-sensitive structure with short direct repeats 5' of Drosophila heat shock genes. Nature. 1983 Aug 11;304(5926):555–557. doi: 10.1038/304555a0. [DOI] [PubMed] [Google Scholar]
  42. Madden S. L., Cook D. M., Morris J. F., Gashler A., Sukhatme V. P., Rauscher F. J., 3rd Transcriptional repression mediated by the WT1 Wilms tumor gene product. Science. 1991 Sep 27;253(5027):1550–1553. doi: 10.1126/science.1654597. [DOI] [PubMed] [Google Scholar]
  43. Maheswaran S., Park S., Bernard A., Morris J. F., Rauscher F. J., 3rd, Hill D. E., Haber D. A. Physical and functional interaction between WT1 and p53 proteins. Proc Natl Acad Sci U S A. 1993 Jun 1;90(11):5100–5104. doi: 10.1073/pnas.90.11.5100. [DOI] [PMC free article] [PubMed] [Google Scholar]
  44. Masuda H., Miller C., Koeffler H. P., Battifora H., Cline M. J. Rearrangement of the p53 gene in human osteogenic sarcomas. Proc Natl Acad Sci U S A. 1987 Nov;84(21):7716–7719. doi: 10.1073/pnas.84.21.7716. [DOI] [PMC free article] [PubMed] [Google Scholar]
  45. McDonnell T. J., Deane N., Platt F. M., Nunez G., Jaeger U., McKearn J. P., Korsmeyer S. J. bcl-2-immunoglobulin transgenic mice demonstrate extended B cell survival and follicular lymphoproliferation. Cell. 1989 Apr 7;57(1):79–88. doi: 10.1016/0092-8674(89)90174-8. [DOI] [PubMed] [Google Scholar]
  46. McDonnell T. J., Korsmeyer S. J. Progression from lymphoid hyperplasia to high-grade malignant lymphoma in mice transgenic for the t(14; 18). Nature. 1991 Jan 17;349(6306):254–256. doi: 10.1038/349254a0. [DOI] [PubMed] [Google Scholar]
  47. McKeon C., Schmidt A., de Crombrugghe B. A sequence conserved in both the chicken and mouse alpha 2(I) collagen promoter contains sites sensitive to S1 nuclease. J Biol Chem. 1984 May 25;259(10):6636–6640. [PubMed] [Google Scholar]
  48. Miura M., Zhu H., Rotello R., Hartwieg E. A., Yuan J. Induction of apoptosis in fibroblasts by IL-1 beta-converting enzyme, a mammalian homolog of the C. elegans cell death gene ced-3. Cell. 1993 Nov 19;75(4):653–660. doi: 10.1016/0092-8674(93)90486-a. [DOI] [PubMed] [Google Scholar]
  49. Mundlos S., Pelletier J., Darveau A., Bachmann M., Winterpacht A., Zabel B. Nuclear localization of the protein encoded by the Wilms' tumor gene WT1 in embryonic and adult tissues. Development. 1993 Dec;119(4):1329–1341. doi: 10.1242/dev.119.4.1329. [DOI] [PubMed] [Google Scholar]
  50. Nakagama H., Heinrich G., Pelletier J., Housman D. E. Sequence and structural requirements for high-affinity DNA binding by the WT1 gene product. Mol Cell Biol. 1995 Mar;15(3):1489–1498. doi: 10.1128/mcb.15.3.1489. [DOI] [PMC free article] [PubMed] [Google Scholar]
  51. Norton P. A., Coffin J. M. Bacterial beta-galactosidase as a marker of Rous sarcoma virus gene expression and replication. Mol Cell Biol. 1985 Feb;5(2):281–290. doi: 10.1128/mcb.5.2.281. [DOI] [PMC free article] [PubMed] [Google Scholar]
  52. Oberhammer F. A., Pavelka M., Sharma S., Tiefenbacher R., Purchio A. F., Bursch W., Schulte-Hermann R. Induction of apoptosis in cultured hepatocytes and in regressing liver by transforming growth factor beta 1. Proc Natl Acad Sci U S A. 1992 Jun 15;89(12):5408–5412. doi: 10.1073/pnas.89.12.5408. [DOI] [PMC free article] [PubMed] [Google Scholar]
  53. Panayotatos N., Wells R. D. Cruciform structures in supercoiled DNA. Nature. 1981 Feb 5;289(5797):466–470. doi: 10.1038/289466a0. [DOI] [PubMed] [Google Scholar]
  54. Park S., Bernard A., Bove K. E., Sens D. A., Hazen-Martin D. J., Garvin A. J., Haber D. A. Inactivation of WT1 in nephrogenic rests, genetic precursors to Wilms' tumour. Nat Genet. 1993 Dec;5(4):363–367. doi: 10.1038/ng1293-363. [DOI] [PubMed] [Google Scholar]
  55. Park S., Schalling M., Bernard A., Maheswaran S., Shipley G. C., Roberts D., Fletcher J., Shipman R., Rheinwald J., Demetri G. The Wilms tumour gene WT1 is expressed in murine mesoderm-derived tissues and mutated in a human mesothelioma. Nat Genet. 1993 Aug;4(4):415–420. doi: 10.1038/ng0893-415. [DOI] [PubMed] [Google Scholar]
  56. Pelletier J., Bruening W., Kashtan C. E., Mauer S. M., Manivel J. C., Striegel J. E., Houghton D. C., Junien C., Habib R., Fouser L. Germline mutations in the Wilms' tumor suppressor gene are associated with abnormal urogenital development in Denys-Drash syndrome. Cell. 1991 Oct 18;67(2):437–447. doi: 10.1016/0092-8674(91)90194-4. [DOI] [PubMed] [Google Scholar]
  57. Pelletier J., Schalling M., Buckler A. J., Rogers A., Haber D. A., Housman D. Expression of the Wilms' tumor gene WT1 in the murine urogenital system. Genes Dev. 1991 Aug;5(8):1345–1356. doi: 10.1101/gad.5.8.1345. [DOI] [PubMed] [Google Scholar]
  58. Petch L. A., Harris J., Raymond V. W., Blasband A., Lee D. C., Earp H. S. A truncated, secreted form of the epidermal growth factor receptor is encoded by an alternatively spliced transcript in normal rat tissue. Mol Cell Biol. 1990 Jun;10(6):2973–2982. doi: 10.1128/mcb.10.6.2973. [DOI] [PMC free article] [PubMed] [Google Scholar]
  59. Pritchard-Jones K., Fleming S., Davidson D., Bickmore W., Porteous D., Gosden C., Bard J., Buckler A., Pelletier J., Housman D. The candidate Wilms' tumour gene is involved in genitourinary development. Nature. 1990 Jul 12;346(6280):194–197. doi: 10.1038/346194a0. [DOI] [PubMed] [Google Scholar]
  60. Pulleyblank D. E., Haniford D. B., Morgan A. R. A structural basis for S1 nuclease sensitivity of double-stranded DNA. Cell. 1985 Aug;42(1):271–280. doi: 10.1016/s0092-8674(85)80122-7. [DOI] [PubMed] [Google Scholar]
  61. Rauscher F. J., 3rd, Morris J. F., Tournay O. E., Cook D. M., Curran T. Binding of the Wilms' tumor locus zinc finger protein to the EGR-1 consensus sequence. Science. 1990 Nov 30;250(4985):1259–1262. doi: 10.1126/science.2244209. [DOI] [PubMed] [Google Scholar]
  62. Reddy J. C., Morris J. C., Wang J., English M. A., Haber D. A., Shi Y., Licht J. D. WT1-mediated transcriptional activation is inhibited by dominant negative mutant proteins. J Biol Chem. 1995 May 5;270(18):10878–10884. doi: 10.1074/jbc.270.18.10878. [DOI] [PubMed] [Google Scholar]
  63. Rogers S. A., Ryan G., Hammerman M. R. Metanephric transforming growth factor-alpha is required for renal organogenesis in vitro. Am J Physiol. 1992 Apr;262(4 Pt 2):F533–F539. doi: 10.1152/ajprenal.1992.262.4.F533. [DOI] [PubMed] [Google Scholar]
  64. Sharma P. M., Yang X., Bowman M., Roberts V., Sukumar S. Molecular cloning of rat Wilms' tumor complementary DNA and a study of messenger RNA expression in the urogenital system and the brain. Cancer Res. 1992 Nov 15;52(22):6407–6412. [PubMed] [Google Scholar]
  65. Smith C. A., Williams G. T., Kingston R., Jenkinson E. J., Owen J. J. Antibodies to CD3/T-cell receptor complex induce death by apoptosis in immature T cells in thymic cultures. Nature. 1989 Jan 12;337(6203):181–184. doi: 10.1038/337181a0. [DOI] [PubMed] [Google Scholar]
  66. Strasser A., Harris A. W., Cory S. bcl-2 transgene inhibits T cell death and perturbs thymic self-censorship. Cell. 1991 Nov 29;67(5):889–899. doi: 10.1016/0092-8674(91)90362-3. [DOI] [PubMed] [Google Scholar]
  67. Swirnoff A. H., Milbrandt J. DNA-binding specificity of NGFI-A and related zinc finger transcription factors. Mol Cell Biol. 1995 Apr;15(4):2275–2287. doi: 10.1128/mcb.15.4.2275. [DOI] [PMC free article] [PubMed] [Google Scholar]
  68. Templeton D. J., Park S. H., Lanier L., Weinberg R. A. Nonfunctional mutants of the retinoblastoma protein are characterized by defects in phosphorylation, viral oncoprotein association, and nuclear tethering. Proc Natl Acad Sci U S A. 1991 Apr 15;88(8):3033–3037. doi: 10.1073/pnas.88.8.3033. [DOI] [PMC free article] [PubMed] [Google Scholar]
  69. Veis D. J., Sorenson C. M., Shutter J. R., Korsmeyer S. J. Bcl-2-deficient mice demonstrate fulminant lymphoid apoptosis, polycystic kidneys, and hypopigmented hair. Cell. 1993 Oct 22;75(2):229–240. doi: 10.1016/0092-8674(93)80065-m. [DOI] [PubMed] [Google Scholar]
  70. Velu T. J., Beguinot L., Vass W. C., Willingham M. C., Merlino G. T., Pastan I., Lowy D. R. Epidermal-growth-factor-dependent transformation by a human EGF receptor proto-oncogene. Science. 1987 Dec 4;238(4832):1408–1410. doi: 10.1126/science.3500513. [DOI] [PubMed] [Google Scholar]
  71. Voloshin O. N., Mirkin S. M., Lyamichev V. I., Belotserkovskii B. P., Frank-Kamenetskii M. D. Chemical probing of homopurine-homopyrimidine mirror repeats in supercoiled DNA. Nature. 1988 Jun 2;333(6172):475–476. doi: 10.1038/333475a0. [DOI] [PubMed] [Google Scholar]
  72. Wang Z. Y., Madden S. L., Deuel T. F., Rauscher F. J., 3rd The Wilms' tumor gene product, WT1, represses transcription of the platelet-derived growth factor A-chain gene. J Biol Chem. 1992 Nov 5;267(31):21999–22002. [PubMed] [Google Scholar]
  73. Wang Z. Y., Qiu Q. Q., Deuel T. F. The Wilms' tumor gene product WT1 activates or suppresses transcription through separate functional domains. J Biol Chem. 1993 May 5;268(13):9172–9175. [PubMed] [Google Scholar]
  74. Wang Z. Y., Qiu Q. Q., Enger K. T., Deuel T. F. A second transcriptionally active DNA-binding site for the Wilms tumor gene product, WT1. Proc Natl Acad Sci U S A. 1993 Oct 1;90(19):8896–8900. doi: 10.1073/pnas.90.19.8896. [DOI] [PMC free article] [PubMed] [Google Scholar]
  75. Werner H., Re G. G., Drummond I. A., Sukhatme V. P., Rauscher F. J., 3rd, Sens D. A., Garvin A. J., LeRoith D., Roberts C. T., Jr Increased expression of the insulin-like growth factor I receptor gene, IGF1R, in Wilms tumor is correlated with modulation of IGF1R promoter activity by the WT1 Wilms tumor gene product. Proc Natl Acad Sci U S A. 1993 Jun 15;90(12):5828–5832. doi: 10.1073/pnas.90.12.5828. [DOI] [PMC free article] [PubMed] [Google Scholar]
  76. Yonish-Rouach E., Resnitzky D., Lotem J., Sachs L., Kimchi A., Oren M. Wild-type p53 induces apoptosis of myeloid leukaemic cells that is inhibited by interleukin-6. Nature. 1991 Jul 25;352(6333):345–347. doi: 10.1038/352345a0. [DOI] [PubMed] [Google Scholar]
  77. Yu Y. T., Manley J. L. Structure and function of the S1 nuclease-sensitive site in the adenovirus late promoter. Cell. 1986 Jun 6;45(5):743–751. doi: 10.1016/0092-8674(86)90788-9. [DOI] [PubMed] [Google Scholar]