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. 1993 Jan 1;289(Pt 1):133–139. doi: 10.1042/bj2890133

Structural analysis of the human insulin-like growth factor-II P3 promoter.

A M Raizis 1, M R Eccles 1, A E Reeve 1
PMCID: PMC1132140  PMID: 8424751

Abstract

The expression of insulin-like growth factor-II (IGF-II) has been observed previously in many human cancers. The human IGF-II P3 promoter has been shown by others to give rise to abundant 6.0 kb and 2.2 kb fetal transcripts which are expressed in a variety of both paediatric and adult tumours. In order to determine the mechanism by which the P3 promoter is controlled, the promoter was analysed in cell lines using chloramphenicol acetyltransferase (CAT) assay and DNAase I footprinting techniques. The data indicated that P3 is a complex promoter involving at least nine transcription factor binding sites. Furthermore, high levels of 5-methylcytosine detected in the P3 promoter of HeLa genomic DNA suggest that IGF-II gene expression may also be influenced by DNA methylation.

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Selected References

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

  1. Adashi E. Y., Resnick C. E., Rosenfeld R. G. Insulin-like growth factor-I (IGF-I) and IGF-II hormonal action in cultured rat granulosa cells: mediation via type I but not type II IGF receptors. Endocrinology. 1990 Jan;126(1):216–222. doi: 10.1210/endo-126-1-216. [DOI] [PubMed] [Google Scholar]
  2. Antequera F., Boyes J., Bird A. High levels of de novo methylation and altered chromatin structure at CpG islands in cell lines. Cell. 1990 Aug 10;62(3):503–514. doi: 10.1016/0092-8674(90)90015-7. [DOI] [PubMed] [Google Scholar]
  3. Braithwaite A. W., Sturzbecher H. W., Addison C., Palmer C., Rudge K., Jenkins J. R. Mouse p53 inhibits SV40 origin-dependent DNA replication. Nature. 1987 Oct 1;329(6138):458–460. doi: 10.1038/329458a0. [DOI] [PubMed] [Google Scholar]
  4. Briggs M. R., Kadonaga J. T., Bell S. P., Tjian R. Purification and biochemical characterization of the promoter-specific transcription factor, Sp1. Science. 1986 Oct 3;234(4772):47–52. doi: 10.1126/science.3529394. [DOI] [PubMed] [Google Scholar]
  5. Cao X. M., Koski R. A., Gashler A., McKiernan M., Morris C. F., Gaffney R., Hay R. V., Sukhatme V. P. Identification and characterization of the Egr-1 gene product, a DNA-binding zinc finger protein induced by differentiation and growth signals. Mol Cell Biol. 1990 May;10(5):1931–1939. doi: 10.1128/mcb.10.5.1931. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Cariani E., Lasserre C., Seurin D., Hamelin B., Kemeny F., Franco D., Czech M. P., Ullrich A., Brechot C. Differential expression of insulin-like growth factor II mRNA in human primary liver cancers, benign liver tumors, and liver cirrhosis. Cancer Res. 1988 Dec 1;48(23):6844–6849. [PubMed] [Google Scholar]
  7. Chen C., Okayama H. High-efficiency transformation of mammalian cells by plasmid DNA. Mol Cell Biol. 1987 Aug;7(8):2745–2752. doi: 10.1128/mcb.7.8.2745. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Crosby S. D., Puetz J. J., Simburger K. S., Fahrner T. J., Milbrandt J. The early response gene NGFI-C encodes a zinc finger transcriptional activator and is a member of the GCGGGGGCG (GSG) element-binding protein family. Mol Cell Biol. 1991 Aug;11(8):3835–3841. doi: 10.1128/mcb.11.8.3835. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. DeChiara T. M., Efstratiadis A., Robertson E. J. A growth-deficiency phenotype in heterozygous mice carrying an insulin-like growth factor II gene disrupted by targeting. Nature. 1990 May 3;345(6270):78–80. doi: 10.1038/345078a0. [DOI] [PubMed] [Google Scholar]
  10. DeChiara T. M., Robertson E. J., Efstratiadis A. Parental imprinting of the mouse insulin-like growth factor II gene. Cell. 1991 Feb 22;64(4):849–859. doi: 10.1016/0092-8674(91)90513-x. [DOI] [PubMed] [Google Scholar]
  11. Dignam J. D., Lebovitz R. M., Roeder R. G. Accurate transcription initiation by RNA polymerase II in a soluble extract from isolated mammalian nuclei. Nucleic Acids Res. 1983 Mar 11;11(5):1475–1489. doi: 10.1093/nar/11.5.1475. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. El-Badry O. M., Romanus J. A., Helman L. J., Cooper M. J., Rechler M. M., Israel M. A. Autonomous growth of a human neuroblastoma cell line is mediated by insulin-like growth factor II. J Clin Invest. 1989 Sep;84(3):829–839. doi: 10.1172/JCI114243. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Evans T., DeChiara T., Efstratiadis A. A promoter of the rat insulin-like growth factor II gene consists of minimal control elements. J Mol Biol. 1988 Jan 5;199(1):61–81. doi: 10.1016/0022-2836(88)90379-8. [DOI] [PubMed] [Google Scholar]
  14. Favaloro J., Treisman R., Kamen R. Transcription maps of polyoma virus-specific RNA: analysis by two-dimensional nuclease S1 gel mapping. Methods Enzymol. 1980;65(1):718–749. doi: 10.1016/s0076-6879(80)65070-8. [DOI] [PubMed] [Google Scholar]
  15. Ferguson-Smith A. C., Cattanach B. M., Barton S. C., Beechey C. V., Surani M. A. Embryological and molecular investigations of parental imprinting on mouse chromosome 7. Nature. 1991 Jun 20;351(6328):667–670. doi: 10.1038/351667a0. [DOI] [PubMed] [Google Scholar]
  16. Gansler T., Furlanetto R., Gramling T. S., Robinson K. A., Blocker N., Buse M. G., Sens D. A., Garvin A. J. Antibody to type I insulinlike growth factor receptor inhibits growth of Wilms' tumor in culture and in athymic mice. Am J Pathol. 1989 Dec;135(6):961–966. [PMC free article] [PubMed] [Google Scholar]
  17. Ghosh D. A relational database of transcription factors. Nucleic Acids Res. 1990 Apr 11;18(7):1749–1756. doi: 10.1093/nar/18.7.1749. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Gloudemans T., Prinsen I., Van Unnik J. A., Lips C. J., Den Otter W., Sussenbach J. S. Insulin-like growth factor gene expression in human smooth muscle tumors. Cancer Res. 1990 Oct 15;50(20):6689–6695. [PubMed] [Google Scholar]
  19. Gray A., Tam A. W., Dull T. J., Hayflick J., Pintar J., Cavenee W. K., Koufos A., Ullrich A. Tissue-specific and developmentally regulated transcription of the insulin-like growth factor 2 gene. DNA. 1987 Aug;6(4):283–295. doi: 10.1089/dna.1987.6.283. [DOI] [PubMed] [Google Scholar]
  20. Hari J., Pierce S. B., Morgan D. O., Sara V., Smith M. C., Roth R. A. The receptor for insulin-like growth factor II mediates an insulin-like response. EMBO J. 1987 Nov;6(11):3367–3371. doi: 10.1002/j.1460-2075.1987.tb02658.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Haselbacher G. K., Irminger J. C., Zapf J., Ziegler W. H., Humbel R. E. Insulin-like growth factor II in human adrenal pheochromocytomas and Wilms tumors: expression at the mRNA and protein level. Proc Natl Acad Sci U S A. 1987 Feb;84(4):1104–1106. doi: 10.1073/pnas.84.4.1104. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Holthuizen P., van der Lee F. M., Ikejiri K., Yamamoto M., Sussenbach J. S. Identification and initial characterization of a fourth leader exon and promoter of the human IGF-II gene. Biochim Biophys Acta. 1990 Nov 30;1087(3):341–343. doi: 10.1016/0167-4781(90)90010-y. [DOI] [PubMed] [Google Scholar]
  23. Jones K. A., Kadonaga J. T., Rosenfeld P. J., Kelly T. J., Tjian R. A cellular DNA-binding protein that activates eukaryotic transcription and DNA replication. Cell. 1987 Jan 16;48(1):79–89. doi: 10.1016/0092-8674(87)90358-8. [DOI] [PubMed] [Google Scholar]
  24. Lambert S., Vivario J., Boniver J., Gol-Winkler R. Abnormal expression and structural modification of the insulin-like growth-factor-II gene in human colorectal tumors. Int J Cancer. 1990 Sep 15;46(3):405–410. doi: 10.1002/ijc.2910460313. [DOI] [PubMed] [Google Scholar]
  25. 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]
  26. 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]
  27. Matsuguchi T., Takahashi K., Ikejiri K., Ueno T., Endo H., Yamamoto M. Functional analysis of multiple promoters of the rat insulin-like factor II gene. Biochim Biophys Acta. 1990 Apr 6;1048(2-3):165–170. doi: 10.1016/0167-4781(90)90052-4. [DOI] [PubMed] [Google Scholar]
  28. Melton D. A., Krieg P. A., Rebagliati M. R., Maniatis T., Zinn K., Green M. R. Efficient in vitro synthesis of biologically active RNA and RNA hybridization probes from plasmids containing a bacteriophage SP6 promoter. Nucleic Acids Res. 1984 Sep 25;12(18):7035–7056. doi: 10.1093/nar/12.18.7035. [DOI] [PMC free article] [PubMed] [Google Scholar]
  29. Nehlin J. O., Ronne H. Yeast MIG1 repressor is related to the mammalian early growth response and Wilms' tumour finger proteins. EMBO J. 1990 Sep;9(9):2891–2898. doi: 10.1002/j.1460-2075.1990.tb07479.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  30. Nielsen F. C., Gammeltoft S., Christiansen J. Translational discrimination of mRNAs coding for human insulin-like growth factor II. J Biol Chem. 1990 Aug 15;265(23):13431–13434. [PubMed] [Google Scholar]
  31. Ohlsson R., Holmgren L., Glaser A., Szpecht A., Pfeifer-Ohlsson S. Insulin-like growth factor 2 and short-range stimulatory loops in control of human placental growth. EMBO J. 1989 Jul;8(7):1993–1999. doi: 10.1002/j.1460-2075.1989.tb03606.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  32. 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]
  33. Reeve A. E., Eccles M. R., Wilkins R. J., Bell G. I., Millow L. J. Expression of insulin-like growth factor-II transcripts in Wilms' tumour. Nature. 1985 Sep 19;317(6034):258–260. doi: 10.1038/317258a0. [DOI] [PubMed] [Google Scholar]
  34. Sandberg A. C., Engberg C., Lake M., von Holst H., Sara V. R. The expression of insulin-like growth factor I and insulin-like growth factor II genes in the human fetal and adult brain and in glioma. Neurosci Lett. 1988 Oct 31;93(1):114–119. doi: 10.1016/0304-3940(88)90022-5. [DOI] [PubMed] [Google Scholar]
  35. Scott J., Cowell J., Robertson M. E., Priestley L. M., Wadey R., Hopkins B., Pritchard J., Bell G. I., Rall L. B., Graham C. F. Insulin-like growth factor-II gene expression in Wilms' tumour and embryonic tissues. Nature. 1985 Sep 19;317(6034):260–262. doi: 10.1038/317260a0. [DOI] [PubMed] [Google Scholar]
  36. Su T. S., Liu W. Y., Han S. H., Jansen M., Yang-Fen T. L., P'eng F. K., Chou C. K. Transcripts of the insulin-like growth factors I and II in human hepatoma. Cancer Res. 1989 Apr 1;49(7):1773–1777. [PubMed] [Google Scholar]
  37. Thompson M. A., Cox A. J., Whitehead R. H., Jonas H. A. Autocrine regulation of human tumor cell proliferation by insulin-like growth factor II: an in-vitro model. Endocrinology. 1990 Jun;126(6):3033–3042. doi: 10.1210/endo-126-6-3033. [DOI] [PubMed] [Google Scholar]
  38. Tollefsen S. E., Sadow J. L., Rotwein P. Coordinate expression of insulin-like growth factor II and its receptor during muscle differentiation. Proc Natl Acad Sci U S A. 1989 Mar;86(5):1543–1547. doi: 10.1073/pnas.86.5.1543. [DOI] [PMC free article] [PubMed] [Google Scholar]
  39. Tricoli J. V., Rall L. B., Karakousis C. P., Herrera L., Petrelli N. J., Bell G. I., Shows T. B. Enhanced levels of insulin-like growth factor messenger RNA in human colon carcinomas and liposarcomas. Cancer Res. 1986 Dec;46(12 Pt 1):6169–6173. [PubMed] [Google Scholar]
  40. Yee D., Cullen K. J., Paik S., Perdue J. F., Hampton B., Schwartz A., Lippman M. E., Rosen N. Insulin-like growth factor II mRNA expression in human breast cancer. Cancer Res. 1988 Dec 1;48(23):6691–6696. [PubMed] [Google Scholar]
  41. de Pagter-Holthuizen P., Jansen M., van Schaik F. M., van der Kammen R., Oosterwijk C., Van den Brande J. L., Sussenbach J. S. The human insulin-like growth factor II gene contains two development-specific promoters. FEBS Lett. 1987 Apr 20;214(2):259–264. doi: 10.1016/0014-5793(87)80066-2. [DOI] [PubMed] [Google Scholar]
  42. de Pagter-Holthuizen P., Jansen M., van der Kammen R. A., van Schaik F. M., Sussenbach J. S. Differential expression of the human insulin-like growth factor II gene. Characterization of the IGF-II mRNAs and an mRNA encoding a putative IGF-II-associated protein. Biochim Biophys Acta. 1988 Sep 7;950(3):282–295. doi: 10.1016/0167-4781(88)90124-8. [DOI] [PubMed] [Google Scholar]
  43. van Dijk M. A., van Schaik F. M., Bootsma H. J., Holthuizen P., Sussenbach J. S. Initial characterization of the four promoters of the human insulin-like growth factor II gene. Mol Cell Endocrinol. 1991 Oct;81(1-3):81–94. doi: 10.1016/0303-7207(91)90207-9. [DOI] [PubMed] [Google Scholar]

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