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. 1991 Feb 1;88(3):829–833. doi: 10.1073/pnas.88.3.829

Rapid induction of the c-jun protooncogene in the avian oviduct by the antiestrogen tamoxifen.

C K Lau 1, M Subramaniam 1, K Rasmussen 1, T C Spelsberg 1
PMCID: PMC50907  PMID: 1704133

Abstract

This report describes a rapid regulation of the expression of the c-jun protooncogene by the antiestrogen tamoxifen (Tam). The c-jun protooncogene codes for an important component of the AP-1 transcription factor complex, which regulates the expression of many unlinked genes. Repeated experiments have shown that Tam rapidly increases the steady-state c-jun mRNA levels in the avian oviduct but decreases the levels in the liver. The Tam effects are time- and dose-dependent. These results are supported by other studies that have demonstrated that 17 beta-estradiol decreases steady-state levels of c-jun protooncogene mRNA in oviducts of animals fully withdrawn from estradiol. The effect of Tam in the avian oviduct is in contrast to the reported effects of Tam on the expression of practically all other genes in the avian oviduct and other animal tissues. Transcription analyses using nuclear runoff experiments with oviduct nuclei demonstrate a decrease in the c-jun gene transcription within minutes after Tam treatment with a return to 75% of control values by 4 hr. The fact that Tam transiently decreases the transcription of the c-jun gene but increases the steady-state c-jun mRNA levels suggests that Tam must alter both transcriptional and post-transcriptional events. The results support a role of the c-jun protooncogene as a regulatory gene in the cascade model for steroid action whereby steroids rapidly regulate the regulatory genes, which in turn regulate many other structural genes.

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Selected References

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

  1. Angel P., Allegretto E. A., Okino S. T., Hattori K., Boyle W. J., Hunter T., Karin M. Oncogene jun encodes a sequence-specific trans-activator similar to AP-1. Nature. 1988 Mar 10;332(6160):166–171. doi: 10.1038/332166a0. [DOI] [PubMed] [Google Scholar]
  2. Bohmann D., Bos T. J., Admon A., Nishimura T., Vogt P. K., Tjian R. Human proto-oncogene c-jun encodes a DNA binding protein with structural and functional properties of transcription factor AP-1. Science. 1987 Dec 4;238(4832):1386–1392. doi: 10.1126/science.2825349. [DOI] [PubMed] [Google Scholar]
  3. Bos T. J., Bohmann D., Tsuchie H., Tjian R., Vogt P. K. v-jun encodes a nuclear protein with enhancer binding properties of AP-1. Cell. 1988 Mar 11;52(5):705–712. doi: 10.1016/0092-8674(88)90408-4. [DOI] [PubMed] [Google Scholar]
  4. Brelvi Z. S., Studzinski G. P. Inhibition of DNA synthesis by an inducer of differentiation of leukemic cells, 1 alpha, 25 dihydroxy vitamin D3, precedes down regulation of the c-myc gene. J Cell Physiol. 1986 Aug;128(2):171–179. doi: 10.1002/jcp.1041280206. [DOI] [PubMed] [Google Scholar]
  5. Brown A. M., Jeltsch J. M., Roberts M., Chambon P. Activation of pS2 gene transcription is a primary response to estrogen in the human breast cancer cell line MCF-7. Proc Natl Acad Sci U S A. 1984 Oct;81(20):6344–6348. doi: 10.1073/pnas.81.20.6344. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Chen C. L., Feigelson P. Cycloheximide inhibition of hormonal induction of alpha 2u-globulin mRNA. Proc Natl Acad Sci U S A. 1979 Jun;76(6):2669–2673. doi: 10.1073/pnas.76.6.2669. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Cheng S. V., Pollard J. W. c-rasH and ornithine decarboxylase are induced by oestradiol-17 beta in the mouse uterine luminal epithelium independently of the proliferative status of the cell. FEBS Lett. 1986 Feb 17;196(2):309–314. doi: 10.1016/0014-5793(86)80269-1. [DOI] [PubMed] [Google Scholar]
  8. Chirgwin J. M., Przybyla A. E., MacDonald R. J., Rutter W. J. Isolation of biologically active ribonucleic acid from sources enriched in ribonuclease. Biochemistry. 1979 Nov 27;18(24):5294–5299. doi: 10.1021/bi00591a005. [DOI] [PubMed] [Google Scholar]
  9. Coezy E., Borgna J. L., Rochefort H. Tamoxifen and metabolites in MCF7 cells: correlation between binding to estrogen receptor and inhibition of cell growth. Cancer Res. 1982 Jan;42(1):317–323. [PubMed] [Google Scholar]
  10. Curran T., Franza B. R., Jr Fos and Jun: the AP-1 connection. Cell. 1988 Nov 4;55(3):395–397. doi: 10.1016/0092-8674(88)90024-4. [DOI] [PubMed] [Google Scholar]
  11. DeAngelo A. B., Gorski J. Role of RNA synthesis in the estrogen induction of a specific uterine protein. Proc Natl Acad Sci U S A. 1970 Jul;66(3):693–700. doi: 10.1073/pnas.66.3.693. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Dubik D., Dembinski T. C., Shiu R. P. Stimulation of c-myc oncogene expression associated with estrogen-induced proliferation of human breast cancer cells. Cancer Res. 1987 Dec 15;47(24 Pt 1):6517–6521. [PubMed] [Google Scholar]
  13. Eastman-Reks S. B., Vedeckis W. V. Glucocorticoid inhibition of c-myc, c-myb, and c-Ki-ras expression in a mouse lymphoma cell line. Cancer Res. 1986 May;46(5):2457–2462. [PubMed] [Google Scholar]
  14. Elder P. K., Schmidt L. J., Ono T., Getz M. J. Specific stimulation of actin gene transcription by epidermal growth factor and cycloheximide. Proc Natl Acad Sci U S A. 1984 Dec;81(23):7476–7480. doi: 10.1073/pnas.81.23.7476. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Fink K. L., Wieben E. D., Woloschak G. E., Spelsberg T. C. Rapid regulation of c-myc protooncogene expression by progesterone in the avian oviduct. Proc Natl Acad Sci U S A. 1988 Mar;85(6):1796–1800. doi: 10.1073/pnas.85.6.1796. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Forsthoefel A. M., Thompson E. A. Glucocorticoid regulation of transcription of the c-myc cellular protooncogene in P1798 cells. Mol Endocrinol. 1987 Dec;1(12):899–907. doi: 10.1210/mend-1-12-899. [DOI] [PubMed] [Google Scholar]
  17. Fort P., Marty L., Piechaczyk M., el Sabrouty S., Dani C., Jeanteur P., Blanchard J. M. Various rat adult tissues express only one major mRNA species from the glyceraldehyde-3-phosphate-dehydrogenase multigenic family. Nucleic Acids Res. 1985 Mar 11;13(5):1431–1442. doi: 10.1093/nar/13.5.1431. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Katzenellenbogen J. A., Carlson K. E., Katzenellenbogen B. S. Facile geometric isomerization of phenolic non-steroidal estrogens and antiestrogens: limitations to the interpretation of experiments characterizing the activity of individual isomers. J Steroid Biochem. 1985 May;22(5):589–596. doi: 10.1016/0022-4731(85)90210-9. [DOI] [PubMed] [Google Scholar]
  19. Kelly K., Siebenlist U. The regulation and expression of c-myc in normal and malignant cells. Annu Rev Immunol. 1986;4:317–338. doi: 10.1146/annurev.iy.04.040186.001533. [DOI] [PubMed] [Google Scholar]
  20. Knabbe C., Lippman M. E., Wakefield L. M., Flanders K. C., Kasid A., Derynck R., Dickson R. B. Evidence that transforming growth factor-beta is a hormonally regulated negative growth factor in human breast cancer cells. Cell. 1987 Feb 13;48(3):417–428. doi: 10.1016/0092-8674(87)90193-0. [DOI] [PubMed] [Google Scholar]
  21. Lamph W. W., Wamsley P., Sassone-Corsi P., Verma I. M. Induction of proto-oncogene JUN/AP-1 by serum and TPA. Nature. 1988 Aug 18;334(6183):629–631. doi: 10.1038/334629a0. [DOI] [PubMed] [Google Scholar]
  22. Lau C. K., Subramaniam M., Rasmussen K., Spelsberg T. C. Rapid inhibition of the c-jun proto-oncogene expression in avian oviduct by estrogen. Endocrinology. 1990 Nov;127(5):2595–2597. doi: 10.1210/endo-127-5-2595. [DOI] [PubMed] [Google Scholar]
  23. Lippman M. E., Dickson R. B., Gelmann E. P., Rosen N., Knabbe C., Bates S., Bronzert D., Huff K., Kasid A. Growth regulatory peptide production by human breast carcinoma cells. J Steroid Biochem. 1988;30(1-6):53–61. doi: 10.1016/0022-4731(88)90076-3. [DOI] [PubMed] [Google Scholar]
  24. Liu S. C., Sanfilippo B., Perroteau I., Derynck R., Salomon D. S., Kidwell W. R. Expression of transforming growth factor alpha (TGF alpha) in differentiated rat mammary tumors: estrogen induction of TGF alpha production. Mol Endocrinol. 1987 Oct;1(10):683–692. doi: 10.1210/mend-1-10-683. [DOI] [PubMed] [Google Scholar]
  25. Maki Y., Bos T. J., Davis C., Starbuck M., Vogt P. K. Avian sarcoma virus 17 carries the jun oncogene. Proc Natl Acad Sci U S A. 1987 May;84(9):2848–2852. doi: 10.1073/pnas.84.9.2848. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. McMaster G. K., Carmichael G. G. Analysis of single- and double-stranded nucleic acids on polyacrylamide and agarose gels by using glyoxal and acridine orange. Proc Natl Acad Sci U S A. 1977 Nov;74(11):4835–4838. doi: 10.1073/pnas.74.11.4835. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. Mulvihill E. R., Palmiter R. D. Relationship of nuclear estrogen receptor levels to induction of ovalbumin and conalbumin mRNA in chick oviduct. J Biol Chem. 1977 Mar 25;252(6):2060–2068. [PubMed] [Google Scholar]
  28. Mulvihill E. R., Palmiter R. D. Relationship of nuclear progesterone receptors to induction of ovalbumin and conalbumin mRNA in chick oviduct. J Biol Chem. 1980 Mar 10;255(5):2085–2091. [PubMed] [Google Scholar]
  29. Murphy L. C., Dotzlaw H. Regulation of transforming growth factor alpha and transforming growth factor beta messenger ribonucleic acid abundance in T-47D, human breast cancer cells. Mol Endocrinol. 1989 Apr;3(4):611–617. doi: 10.1210/mend-3-4-611. [DOI] [PubMed] [Google Scholar]
  30. Murphy L. J., Murphy L. C., Friesen H. G. Estrogen induction of N-myc and c-myc proto-oncogene expression in the rat uterus. Endocrinology. 1987 May;120(5):1882–1888. doi: 10.1210/endo-120-5-1882. [DOI] [PubMed] [Google Scholar]
  31. Norris J. S., Cornett L. E., Hardin J. W., Kohler P. O., MacLeod S. L., Srivastava A., Syms A. J., Smith R. G. Autocrine regulation of growth: II. Glucocorticoids inhibit transcription of c-sis oncogene-specific RNA transcripts. Biochem Biophys Res Commun. 1984 Jul 18;122(1):124–128. doi: 10.1016/0006-291x(84)90448-0. [DOI] [PubMed] [Google Scholar]
  32. O'Malley B. W., McGuire W. L., Kohler P. O., Korenman S. G. Studies on the mechanism of steroid hormone regulation of synthesis of specific proteins. Recent Prog Horm Res. 1969;25:105–160. doi: 10.1016/b978-0-12-571125-8.50006-5. [DOI] [PubMed] [Google Scholar]
  33. Pertovaara L., Sistonen L., Bos T. J., Vogt P. K., Keski-Oja J., Alitalo K. Enhanced jun gene expression is an early genomic response to transforming growth factor beta stimulation. Mol Cell Biol. 1989 Mar;9(3):1255–1262. doi: 10.1128/mcb.9.3.1255. [DOI] [PMC free article] [PubMed] [Google Scholar]
  34. Quantin B., Breathnach R. Epidermal growth factor stimulates transcription of the c-jun proto-oncogene in rat fibroblasts. Nature. 1988 Aug 11;334(6182):538–539. doi: 10.1038/334538a0. [DOI] [PubMed] [Google Scholar]
  35. Reitsma P. H., Rothberg P. G., Astrin S. M., Trial J., Bar-Shavit Z., Hall A., Teitelbaum S. L., Kahn A. J. Regulation of myc gene expression in HL-60 leukaemia cells by a vitamin D metabolite. Nature. 1983 Dec 1;306(5942):492–494. doi: 10.1038/306492a0. [DOI] [PubMed] [Google Scholar]
  36. Rempel S. A., Johnston R. N. Steroid-induced cell proliferation in vivo is associated with increased c-myc proto-oncogene transcript abundance. Development. 1988 Sep;104(1):87–95. doi: 10.1242/dev.104.1.87. [DOI] [PubMed] [Google Scholar]
  37. Rories C., Lau C. K., Fink K., Spelsberg T. C. Rapid inhibition of c-myc gene expression by a glucocorticoid in the avian oviduct. Mol Endocrinol. 1989 Jun;3(6):991–1001. doi: 10.1210/mend-3-6-991. [DOI] [PubMed] [Google Scholar]
  38. Rories C., Spelsberg T. C. Ovarian steroid action on gene expression: mechanisms and models. Annu Rev Physiol. 1989;51:653–681. doi: 10.1146/annurev.ph.51.030189.003253. [DOI] [PubMed] [Google Scholar]
  39. Ryder K., Lau L. F., Nathans D. A gene activated by growth factors is related to the oncogene v-jun. Proc Natl Acad Sci U S A. 1988 Mar;85(5):1487–1491. doi: 10.1073/pnas.85.5.1487. [DOI] [PMC free article] [PubMed] [Google Scholar]
  40. Ryder K., Nathans D. Induction of protooncogene c-jun by serum growth factors. Proc Natl Acad Sci U S A. 1988 Nov;85(22):8464–8467. doi: 10.1073/pnas.85.22.8464. [DOI] [PMC free article] [PubMed] [Google Scholar]
  41. Sassone-Corsi P., Ransone L. J., Lamph W. W., Verma I. M. Direct interaction between fos and jun nuclear oncoproteins: role of the 'leucine zipper' domain. Nature. 1988 Dec 15;336(6200):692–695. doi: 10.1038/336692a0. [DOI] [PubMed] [Google Scholar]
  42. Southern E. M. Detection of specific sequences among DNA fragments separated by gel electrophoresis. J Mol Biol. 1975 Nov 5;98(3):503–517. doi: 10.1016/s0022-2836(75)80083-0. [DOI] [PubMed] [Google Scholar]
  43. Spelsberg T. C., Littlefield B. A., Seelke R., Dani G. M., Toyoda H., Boyd-Leinen P., Thrall C., Kon O. L. Role of specific chromosomal proteins and DNA sequences in the nuclear binding sites for steroid receptors. Recent Prog Horm Res. 1983;39:463–517. doi: 10.1016/b978-0-12-571139-5.50016-1. [DOI] [PubMed] [Google Scholar]
  44. Sutherland R., Mester J., Baulieu E. E. Tamoxifen is a potent "pure" anti-oestrogen in chick oviduct. Nature. 1977 Jun 2;267(5610):434–435. doi: 10.1038/267434a0. [DOI] [PubMed] [Google Scholar]
  45. Tate A. C., Greene G. L., DeSombre E. R., Jensen E. V., Jordan V. C. Differences between estrogen- and antiestrogen-estrogen receptor complexes from human breast tumors identified with an antibody raised against the estrogen receptor. Cancer Res. 1984 Mar;44(3):1012–1018. [PubMed] [Google Scholar]
  46. Travers M. T., Knowler J. T. Oestrogen-induced expression of oncogenes in the immature rat uterus. FEBS Lett. 1987 Jan 19;211(1):27–30. doi: 10.1016/0014-5793(87)81267-x. [DOI] [PubMed] [Google Scholar]
  47. Varmus H. E. The molecular genetics of cellular oncogenes. Annu Rev Genet. 1984;18:553–612. doi: 10.1146/annurev.ge.18.120184.003005. [DOI] [PubMed] [Google Scholar]
  48. Webb D. K., Moulton B. C., Khan S. A. Estrogen induced expression of the C-jun proto-oncogene in the immature and mature rat uterus. Biochem Biophys Res Commun. 1990 Apr 30;168(2):721–726. doi: 10.1016/0006-291x(90)92381-9. [DOI] [PubMed] [Google Scholar]
  49. Wu B. Y., Fodor E. J., Edwards R. H., Rutter W. J. Nerve growth factor induces the proto-oncogene c-jun in PC12 cells. J Biol Chem. 1989 May 25;264(15):9000–9003. [PubMed] [Google Scholar]

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