Skip to main content
SpringerLink
Log in

Interactions of Estrogens, Protooncogenes and Growth Factors

  • Chapter
Book cover Cellular Signals Controlling Uterine Function

  • 54 Accesses

Summary

The uterus contains EGF receptors and these are regulated in vivo by estrogens. This regulation occurs at the transcriptional level, at least in part. Treatment of immature rats with estradiol also increases uterine levels of several nuclear protooncogenes including c-fos and c-myc. Considerable evidence suggests that this regulation occurs via interaction of occupied tissue estrogen receptors with an estrogen responsive element located in the 5’ upstream region of the fos gene. Based on these results and the work of other laboratories, we propose an overall model for the estrogen control of uterine growth which is similar to the competence/progression model of growth postulated for cultured fibroblasts. In this model the induction of nuclear protooncogenes, which presumably serve as transcription factors, and peptide growth factors/receptors are two distinct mechanisms for amplifying the signal resulting from the interaction of estrogen with its cognate receptor.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 39.99
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 54.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. Alt, F.W., Harlow, E., and Ziff, E.B., Nuclear Oncogenes, Cold Spring Harbor Laboratory, Cold Spring Harbor, New York. (1987).

    Google Scholar 

  2. Anderson, J.N., Clark, J.H., and Peck, E.J., Jr., The relationship between nuclear receptor estrogen binding and uterotrophic responses, Biochem. Biophys. Res. Commun., 48:1460 (1972).

    CAS  Google Scholar 

  3. Anderson, J.N., Peck, E.J., Jr. and Clark, J.H., Nuclear receptor estrogen complex: relationship between concentration and early uterotrophic responses. Endocr. 92:1488 (1973).

    Article  CAS  Google Scholar 

  4. Beato, M., Gene regulation by steroid hormones, Cell 56:335 (1989).

    Article  PubMed  CAS  Google Scholar 

  5. Berk, B.C., Brock, T.A., Webb, R.C., Taubman, M.B., Atkinson, W.J., Gimbrone, M.A., Jr., and Alexander, R.W., Epidermal growth factor, a vascular smooth muscle mitogen, induces rat aortic contraction, J. Clin. Invest. 75:1083 (1985).

    Article  PubMed  CAS  Google Scholar 

  6. Bhargava, G., Rifas, L., and Makman, M.H., Presence of epidermal growth factor receptors and influence of epidermal growth factor on proliferation and aging in cultured smooth muscle cells, J. Cell. Physiol. 100:365 (1979).

    Article  PubMed  CAS  Google Scholar 

  7. Bishop, J.M., Viral Oncogenes, Cell 42:23 (1985).

    CAS  Google Scholar 

  8. Chegini, N., Rao, C.V., Wakin, N., and Sanfilippo, J., Binding of 125I-epidermal growth factor in human uterus, Cell Tissue Res. 246:543 (1986).

    Article  PubMed  CAS  Google Scholar 

  9. Chiu, R., Boyle, W.J., Meek, J., Smeol, T., Hunter, T. and Karin, M., Thec-fos protein interacts with CJun/AP-1 to stimulate transcription of AP-1 responsive genes, cell 54:541 (1988).

    CAS  Google Scholar 

  10. Cohen, S.G., Isolation of a mouse submaxillary protein accelerating incision eruption and eyelid opening in the newborn animal, J. Biol. Chem. 237:1555 (1962).

    PubMed  CAS  Google Scholar 

  11. Deuel, T.F., Polypeptide growth factors: roles in normal and abnormal cell growth, Ann. Rev. Cell Biol. 3:443 (1987).

    Article  PubMed  CAS  Google Scholar 

  12. DiAugustine, R.P., Petrusz, P., Bell, G.I., Brown, C.F., Korach, K.S., McLachlan, J.A., and Teng, C.T., Influence of estrogen on mouse uterine epidermal growth factor precursor protein and messenger ribonucleic acid, Endocr. 122:2355 (1988).

    Article  CAS  Google Scholar 

  13. Distel, R.J., Ro, H.S., Rosen, B.S., Groves, D.L., and Spiegelman, B.M., Nucleoprotein complexes that regulate gene expression in adipocyte differentiation: direct participation of c-fos, Cell 49:835 (1987).

    Article  PubMed  CAS  Google Scholar 

  14. Gardner, R.M., Kirkland, J.L., Ireland, J.S., and Stancel, G.M., Regulation of the uterine response to estrogen by thyroid hormone, Endocr. 103:1164 (1978).

    Article  CAS  Google Scholar 

  15. Gardner, R.M., Lingham, R.B., and Stancel, G.M., Epidermal growth factor stimulates contractions of the isolated uterus, FASEB J. 1:224 (1987).

    PubMed  CAS  Google Scholar 

  16. Gardner, R.M., Goldsmith, J.R., and Stancel, G.M., Pharmacological characterization of epidermal growth factor (EGF) induced uterine contractions, FASEB J. 2:A1143 (1988).

    Google Scholar 

  17. Gardner, R.M., Verner, G., Kirkland, J.L., and Stancel, G.M., Regulation of EGF receptors by estrogen in the mature rat and during the estrous cycle, J. Ster. Biochem 32:339 (1989).

    Article  CAS  Google Scholar 

  18. Gonzalez, F., Lakshmanan, J., Hoath, S., and Fisher, D.A., Effect of oestradiol-17 on uterine epidermal growth factor concentration in immature mice, Acta Endocr. (Copenhagen) 105:425 (1984).

    CAS  Google Scholar 

  19. Gorski, J. and Gannon, F., Current models of steroid hormone action, a critique, Ann. Rev. Physiol. 38:425 (1976).

    Article  CAS  Google Scholar 

  20. Gregory, H., In vivo aspects of urogastrone-epidermal growth factor, J. Cell Sci.(Suppl.) 3:11 (1985).

    CAS  Google Scholar 

  21. Hamburgh, M., Mendoza, C.A., Burkart, J.G., and Weil, F., Thyroid dependent processes in the developing nervous system, In: Hormones and Development, M. Hamburgh and E.J.W. Banning (eds.), pp. 403–415, Meredith Corp. N.Y. (1971).

    Google Scholar 

  22. Ikeda, T., and Sirbasku, P.A., Purification and properties of a mammary uterine pituitary tumor cell growth factor from pregnant sheep uterus, J. Biol. Chem. 259:4049 (1984).

    PubMed  CAS  Google Scholar 

  23. Imai, Y., Epidermal growth factor in rat uterine luminal fluid, Endocr. 110 (Suppl): 162: (abstr.), (1982).

    Google Scholar 

  24. Jensen, E.V. and DeSombre E.R., Mechanism of action of female sex hormones, Ann. Rev. Biochem. 41:203 (1972).

    Article  PubMed  CAS  Google Scholar 

  25. Kirkland, J.L., Gardner, R.M., Ireland, J.S., and Stance!, G.M., The effect of hypophysectomy on the uterine response to estradiol, Endocr. 101:403 (1977).

    Article  CAS  Google Scholar 

  26. Kirkland, J.L., Gardner, R.M., Mukku, V.R., Aktar, M. and Stancel, G.M., Hormonal control of uterine growth: the effect of hypothyroidism on estrogen stimulated cell division, Endocr. 108:2346 (1981).

    Article  CAS  Google Scholar 

  27. Klein-Hitpass, L., Schorp, M., Wagner, U., and Ryfell, G.U., An estrogen responsive element derived from the 5’ flanking region of xenopus vitellogenin A2 gene functions in transfected human cells, Cell 46:1053 (1986).

    Article  PubMed  CAS  Google Scholar 

  28. Knauer, D.J., Wiley, H.S., and Cunningham, D.B., Relationship between epidermal growth factor receptor occupancy and mitogenic response. Quantitative Analysis Using a Steady State Model System, J. Biol. Chem. 259:5623 (1984).

    PubMed  CAS  Google Scholar 

  29. Lech, K., Anderson, K, and Brent, R., DNA-bound fos proteins activate transcription in yeast, Cell 52:179 (1988).

    Article  PubMed  CAS  Google Scholar 

  30. Lin, T.S., Kirkland, J.L., Mukku, V.R., and Stancel, G.M., Autoradiographic localization of epidermal growth factor binding in individual uterine cell types, Biol Reprod. 38:403 (1988).

    Article  PubMed  CAS  Google Scholar 

  31. Lingham, R.B., Stancel, G.M., and Loose-Mitchell, D.M., Regulation of epidermal growth factor receptor messenger RNA by estrogen, Mol. Endocr. 2:230 (1988).

    CAS  Google Scholar 

  32. Loose-Mitchell, D.S., Chiappetta, C., and Stancel, G.M., Estrogen Regulation c fos Messenger Ribonucleic Acid, Mol. Endocr. 2:946 (1988).

    CAS  Google Scholar 

  33. McLachlan, J.A., DiAugustine, R.P., and Newbold, R.R., Estrogen induced uterine cell proliferation in organ culture is inhibited by antibodies to epidermal growth factor, Prog. of the 69th Ann. Mtg. of the Endocr. Soc., Indianapolis, IN, p. 99 (Abstr. #313) (1987).

    Google Scholar 

  34. Mukku, V.R., and Stancel, G.M., Regulation of uterine epidermal growth factor receptors by estrogen, J. Biol. Chem. 260:9820 (1985).

    PubMed  CAS  Google Scholar 

  35. Mukku, V.R., and Stancel, G.M., Receptors for epidermal growth factor in the rat uterus, Endocr. 117:149 (1985b).

    Article  CAS  Google Scholar 

  36. Muramatsu, I., Hollenberg, M.D., and Lederis, K., Vascular actions of epidermal growth factor-urogastrone: possible relationship to prostaglandin production, Can. J. Physiol. Pharmacol. 36:994 (1985).

    Article  Google Scholar 

  37. Murphy, L.J., Murphy, L.C., and Friesen, H.G., Estrogen induces insulin-like growth factor-1 expression in the rat uterus, Mol. Endocr. 1:445 (1987a).

    Article  CAS  Google Scholar 

  38. Murphy, L.J., Murphy, L.C., and Friesen, H.G., Estrogen induction of n-myc and c-myc protooncogene expression in the rat uterus, Endocr. 120:1882 (1987b).

    Article  CAS  Google Scholar 

  39. Murphy, L.J., and Friesen, H.G., Differential effects of estrogen and growth hormone on uterine and hepatic insulin-like growth factor I gene expression in the ovariectomized hypophysectomized rat, Endocr. 122:325 (1988).

    Article  CAS  Google Scholar 

  40. O’Keefe, E.J., and Pledger, W.J., A model of cell cycle control of sequential events regulated by growth factors, Mol. Cell. Endocr. 31:167 (1983).

    Google Scholar 

  41. Rauscher, F.J. III, Sambucetti, L.C., Curran, T., Distel, R.J., and Speigleman, B.M., A common DNA binding site for fos protein and transcription factor AP-1, cell 52:471–480 (1988).

    CAS  Google Scholar 

  42. Rollins, B.J. and Stiles, C.D., Regulation of c-myc and c-fos proto-oncogene expression by animal cell growth factors, In Vitro, Cell. & Dev. Biol. 24:81 (1988).

    Article  CAS  Google Scholar 

  43. Ronnstrand, L., Beckmann, M.P., Faulders, B., Ostman, A., Ek, B., and Heldin, C.H., Purification of the receptor for PDGF from porcine uterus, J. Biol. Chem. 262:2929 (1987).

    PubMed  CAS  Google Scholar 

  44. Ruther, U., Garber, C., Komitowski, D., Muller, R., and Wagner, E.G., Deregulated cfos expression interferes with normal bone development in transgenic mice, nature 325:412 (1987).

    CAS  Google Scholar 

  45. Ryder, K., Lan, L.F., and Nathans, D., A gene activated by growth factors is related to the oncogene v-jun, Proc. Natl. Acad. Sci. USA 85:1487 (1988).

    Article  PubMed  CAS  Google Scholar 

  46. Simmen, R.C.M., Ko, Y., Liu, X.H., Wilde, M.H., Pope, W.F., and Simmen, F.A., A Uterine cell mitogen distinct from epidermal growth factor in porcine uterine luminal fluids: characterization and partial purification, Biol. Reprod. 38:551 (1988).

    Article  CAS  Google Scholar 

  47. Stiles, C.D., Capone, G.T., Scher, C.D., Antoniades, H.N., Van Wyk, J.J., and Pledger, W.J., Dual control of cell growth by somatomedins and platelet-derived growth factor, Proc. Natl. Acad. Sci. 76:1279 (1979).

    Article  PubMed  CAS  Google Scholar 

  48. Tomooka, Y., DiAugustine, R.P., and McLachlan, J.A., Proliferation of mouse uterine epithelial cells in vitro, Endocr. 118:1011 (1986).

    Article  CAS  Google Scholar 

  49. Travers, M.T., and Knowler, J.T., Oestrogen-induced expression of oncogenes in the immature rat uterus, FEBS Lett. 211:27 (1987).

    Article  PubMed  CAS  Google Scholar 

  50. Treisman, R., Transient accumulation of c-fos RNA following serum stimulation requires a conserved 5’ element and c-fos 3’ sequences, Cell 42:889 (1985).

    Article  PubMed  CAS  Google Scholar 

  51. Weisz, A., and Bresciani, F., Estrogen induces expression of c-fos and c-myc protooncogenes in rat uterus, Mol. Endocr. 2:816 (1988).

    CAS  Google Scholar 

  52. Yamamoto, KR., Steroid receptor regulated transcription of specific genes and gene networks, Ann. Rev. Genetics 19:209 (1985).

    Article  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Pharmacology, University of Texas Medical School at Houston, Houston, Texas, 77225, USA

    G. M. Stancel, C. Chiappetta, R. M. Gardner, S. M. Hyder, R. B. Lingham, D. S. Loose-Mitchell, V. R. Mukku & C. A. Orengo

  2. Division of Endocrinology, Department of Pediatrics, Baylor College of Medicine, Houston, Texas, 77225, USA

    J. L. Kirkland & T. H. Lin

Authors
  1. G. M. Stancel
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. C. Chiappetta
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. R. M. Gardner
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. S. M. Hyder
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. J. L. Kirkland
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. T. H. Lin
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. R. B. Lingham
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. D. S. Loose-Mitchell
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. V. R. Mukku
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. C. A. Orengo
    View author publications

    You can also search for this author in PubMed Google Scholar

Editor information

Editors and Affiliations

  1. Wichita State University, Wichita, Kansas, USA

    Lynn A. Lavia

Rights and permissions

Reprints and permissions

Copyright information

© 1991 Springer Science+Business Media New York

About this chapter

Cite this chapter

Stancel, G.M. et al. (1991). Interactions of Estrogens, Protooncogenes and Growth Factors. In: Lavia, L.A. (eds) Cellular Signals Controlling Uterine Function. Springer, Boston, MA. https://doi.org/10.1007/978-1-4615-3724-3_5

Download citation

  • DOI: https://doi.org/10.1007/978-1-4615-3724-3_5

  • Publisher Name: Springer, Boston, MA

  • Print ISBN: 978-1-4613-6657-7

  • Online ISBN: 978-1-4615-3724-3

  • eBook Packages: Springer Book Archive

Publish with us

Policies and ethics

Search

Navigation