Skip to main content
SpringerLink
Log in

Estrogen and Progesterone Receptor Analysis and Action in Breast Cancer

  • Chapter
Breast Cancer Immunodiagnosis and Immunotherapy

Abstract

The elucidation of the molecular mechanisms responsible for the hormonal regulation of cell proliferation in breast cancer has been the object of intense research. Because most breast cancers are initially dependent upon estrogens for continued growth, much of this research has focused on the role of estrogen receptor (ER) in the control of gene expression and mitosis1, and on its use as marker for hormone responsiveness and prognosis.2 In addition, progesterone receptor (PR), as both a mediator of hormonal responses and as a product of estrogen action on breast cancer cells, has been studied extensively as a tumor marker3 and in terms of its regulation by estrogen agonists and antagonists4. Although its function in breast cancer is unknown, the presence as well as the induction of PR has been coupled to estrogen-induced proliferative responses in breast cancer cells. An improved understanding of the function and regulation of expression of these transcription factors is emerging from studies of the structure, composition and dynamics of the receptor proteins and the genes that encode them. The recent cloning and molecular analysis of all of the known steroid receptors has led to the definition of common functional domains and a proposed mechanism by which they interact with responsive genes, via cis-acting DNA enhancer elements, in normal and neoplastic tissues5. For ER and PR, these studies have been aided by the availability of a number of monoclonal antibody probes directed against specific regions of each receptor6,7. In addition, the same antibodies have been used to develop validated quantitative and histochemical immunoassays for ER and PR in a variety of hormoneresponsive tissues and related cancers8,9,10

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 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. R.B. Dickson, M.E. MacManaway and M.E. Lippman, Estrogen-Induced Factors of Breast Cancer Cells Partially Replace Estrogen to Promote Tumor Growth, Scienc. 232:1540 (1986).

    Article  PubMed  CAS  Google Scholar 

  2. E.R. DeSombre, P.P. Carbonne, E.V. Jensen, W.L. McGuire, S.A. Wells, J.L. Wittliff and M.B. Lipsett, Special Report: Steroid Receptors in Breast Cancer, N. Engl. J. Med. 301: 1011 (1979).

    Article  PubMed  CAS  Google Scholar 

  3. G.M. Clark, W.L McGuire, C.A. Hubay, O.H. Pearson and J.S. Marshall, Progesterone Receptor as a Prognostic Factor in Stage II Breast Cancer, N. Engl. J. Med. 309: 1343 (1983).

    Article  PubMed  CAS  Google Scholar 

  4. L.D. Read, C.E. Snider, J.S. Miller, G.L. Greene and B.S. Katzenellenbogen, Ligand Modulated regulation of Progesterone Receptor Messenger Ribonucleic Acid and Protein in Human Breast Cancer Cell Lines, Mol. Endocrinol. 2: 263 (1988).

    Article  PubMed  CAS  Google Scholar 

  5. R.M. Evans, The Steroid and Thyroid Hormone Receptor Superfamily, Science. 240: 889 (1988).

    Article  PubMed  CAS  Google Scholar 

  6. G.L. Greene, N.B. Sobel, W.J. King and E.V. Jensen, Immunochemical Studies of Estrogen Receptors, J. Steroid Biochem. 20: 51 (1984).

    Article  PubMed  CAS  Google Scholar 

  7. G.L. Greene, K. Harris, R. Bova, R. Kinders, B. Moore and C. Nolan, Purification of T47D Human Progesterone Receptor and Immunochemical Characterization with Monoclonal Antibodies, Mol. Endocrinol. 2: 714 (1988).

    Article  PubMed  CAS  Google Scholar 

  8. G.L. Greene and M.F. Press, Immunochemical Evaluation of Estrogen Receptor and Progesterone Receptor in Breast Cancer, in: “Immunological Approaches to the Diagnosis and Therapy of Breast Cancer”, R. L. Ceriani, ed., Plenum, New York (1987).

    Google Scholar 

  9. M.F. Press and G.L. Greene, Localization of Progesterone Receptor with Monoclonal Antibodies to the Human Progesterone Receptor, Endocrinolog. 122: 1165 (1988).

    Article  PubMed  CAS  Google Scholar 

  10. L.B. Kinsel, J.L. Flowers, J. Konrath, G.S. Leight, G.L. Greene, and K. S. McCarty, Heterogeneity vs Asynchrony of Receptor Expression in Breast Cancer as Determined by Monoclonal Antibodies, in: “Immunological Approaches to the Diagnosis and Therapy of Breast Cancer”, R.L. Ceriani, ed., Plenum, New York (1987).

    Google Scholar 

  11. B. Theveny, A. Bailly, C. Rach, M. Rach, E. Delain, and E. Milgrom, Association of DNABound Progesterone Receptors, Nature. 329: 79 (1987).

    Article  PubMed  CAS  Google Scholar 

  12. D.B. Mendel, J.E. Bodwell, B. Gametchu, R.B. Harrison and A. Munk, Molybate-Stabilized Nonactivated Glucocorticoid-Receptor Complexes Contain a 90-kDa Non-Steroid-Binding Phosphoprotein that is Lost on Activation, J. Biol. Che.. 261: 3758 (1986).

    PubMed  CAS  Google Scholar 

  13. A. Goldberger, B.A. Littlefield, J. Katzman and T.C. Spelsberg, Monoclonal Antibodies recognize the Nuclear Binding Sits of the Avian Oviduct Progesterone Receptor, Endocrinolog. 118: 2235 (1986).

    Article  PubMed  CAS  Google Scholar 

  14. F. Auricchio, A. Migliaccio, M. Di Domenico and E. Nola, Oestradiol Stimulates Tyrosine Phosphorylation and Hormone-OBinding Activity of its Own Receptor in a Cell-free System, EMBO J. 6: 2923 (1987).

    PubMed  CAS  Google Scholar 

  15. H. Loosefelt, F. Logeat, M.T. Vu Hai and E. Milgrom, The Rabbit Progesterone Receptor: Evidence for a Single Steroid-Binding Subunit and Characterization of Receptor mRNA, J. Biol. Chem. 259: 14196 (1984).

    Google Scholar 

  16. G.L. Greene, Estrogen and Progesterone Receptor Composition, Expression and Analysis in Breast Cancer, 60th Annual Meeting of the Endocrine Society, Indianapolis, Abstr. p. 12.

    Google Scholar 

  17. G.L. Greene, P. Gilna, M. Waterfield, A. Baker, Y. Hort and J. Shine, Sequence and Expression of Human Estrogen receptor Complementary DNA, Scienc. 231: 1150 (1986).

    Article  PubMed  CAS  Google Scholar 

  18. S. Okret, L. Poellinger, Y. Dong, and JA Gustafsson, Down-regulation of Glucocorticoid Receptor mRNA by Glucocorticoid Hormones and Recognition by the Receptor of a Specific Binding Sequence Within a Receptor cDNA clone, Proc. Natl. Acad. Sci. US. 83: 5899 (1986).

    Article  PubMed  CAS  Google Scholar 

  19. V. Kumar, S. Green, G. Stack, M. Berry, J.R. Jin and P. Chambon, Functional Domains of the Human Estrogen Receptor, Cell. 51: 941 (1987).

    Article  PubMed  CAS  Google Scholar 

  20. S. Green, V. Kumar, I. Theulaz, W. Wahli and P. Chambon, The N-Terminal DNA-Binding ‘Zinc Finger’ of the Oestrogen and Glucocorticoid Receptors Determines Target Gene Specificity, EMBO J.. 7: 3037 (1988).

    PubMed  CAS  Google Scholar 

  21. L. Klein-Hitpass, G.U. Ryffel, E. Heitlinger and A.C.B. Cato, A 13 bp Palindrome is a Functional Estrogen Responsive Element and Interacts Specifically with Estrogen Receptor, Nuc. Acids. Res. 16: 647 (1988).

    Article  CAS  Google Scholar 

  22. L. Klein-Hitpass, S.Y. Tsai, G.L. Greene, J.H. Clark, M.J. Tsai and B. O’Malley, Specific Binding of Estrogen Receptor to the Estrogen receptor Element, submitted, Mol. Cell. Biol. in press (1988).

    Google Scholar 

  23. M.A. Miller, A. Mullick, G.L. Greene and B. Katzenellenbogen, Characterization of the Subunit Nature of Nuclear Estrogen Receptors by Chemical Cross-linking and Dense Amino Acid Labeling, Endocrinology. 117: 515 (1985).

    Article  PubMed  CAS  Google Scholar 

  24. S. Schuh, W. Yonemoto, J. Brugge, V.J. Baur, R.M. Riehl, W.P. Sullivan and D.O. Toft, A 90,000-Dalton Binding Protein common to both Steroid Receptors and the Rous Sarcoma Virus Transforming Protein pp60 vsrc, J. Biol. Chem. 260:14292 (1985).

    PubMed  CAS  Google Scholar 

  25. A.L. Unger, R. Uppaluri, S. Ahern, J.L. Colby and J.L. Tymoczko, Isolation of Ribonucleic Acid from the Unactivated Rat Liver Glucocorticoid Receptor, Mol. Endocrino.. 2:952 (1988).

    Article  PubMed  CAS  Google Scholar 

  26. D. Picard and K.R. Yamamoto, Two Signals Mediate Hormone-Dependent Nuclear Localization of The Glucocorticoid Receptor, EMBO J. 6:3333 (1987).

    PubMed  CAS  Google Scholar 

  27. M. Misrahi, H. Loosefelt, M. Atger, C. Meriel, V. Zerah, P. Dessen and E. Milgrom, Organization of the Entire Rabbit Progesterone Receptor mRNA and of the Promoter and 5’ Flanking Region of the Gene, Nuc. Acids Res. 16: 5459 (1988).

    Article  CAS  Google Scholar 

  28. P. Gilna, T. Zaruchi-Schulz and G.L. Greene, Cloning and Characterization of Human Progesterone Receptor, 69th Annual Meeting of the Endocrine Society, Indianapolis, Abstr. 1.

    Google Scholar 

  29. M. Misrahi, M. Atger, L. d’Auriol, H. Loosefelt, C. Meriel, F. Fridlansky, A. GuiochonMantel, F. Galibert and E. Milgrom, Complete Amino Acid Sequence of the Human Progesterone Receptor Deduced from Cloned cDNA, Biochem. Biophys. Res. Comm. 143: 740 (1987).

    Article  PubMed  CAS  Google Scholar 

  30. M.A. Carson, M.J. Tsai, O.M. Conneely, B.L. Maxwell, J.H. Clark, A.D. W. Dobson, A. Elbrecht, D.O. Toft, W.T. Schrader and B.W. O’Malley, Structure Function Properties of the Chicken Progesterone Receptor A Syntheisized from Complementary Deoxyribonucleic Acid. Mol. Endocrino.. 1: 791 (1987).

    Article  PubMed  CAS  Google Scholar 

  31. H. Gronemeyer, B. Turcotte, C. Quirin-Stricker, M.T. Bocquel, M.E. Meyer, Z. Krozowski, J.M. Jeltsch, T. Lerouge, J.M. Garnier and P. Chambon, The Chicken Progesterone Receptor: Sequence, Expression and Functional Analysis. EMBO J. 6: 3985 (1987).

    PubMed  CAS  Google Scholar 

  32. K. Rao, W. Piralta, G.L. Greene and C. F. Fox, Cellular Progesterone Receptor Phosphorylation in Response to Ligands Activating Protein Kinases, Biochem. Biophys. Res. Comm. 146:1357 (1987).

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. The Ben May Institute, The University of Chicago, 60637, Chicago, Illinois, USA

    Geoffrey L. Greene & Paul Gilna

  2. Metabolic Research Unit, University of California, 94143, San Francisco, California, USA

    Peter Kushner

Authors
  1. Geoffrey L. Greene
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Paul Gilna
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Peter Kushner
    View author publications

    You can also search for this author in PubMed Google Scholar

Editor information

Editors and Affiliations

  1. John Muir Cancer and Aging Research Institute, Walnut Creek, California, USA

    Roberto L. Ceriani

Rights and permissions

Reprints and permissions

Copyright information

© 1989 Springer Science+Business Media New York

About this chapter

Cite this chapter

Greene, G.L., Gilna, P., Kushner, P. (1989). Estrogen and Progesterone Receptor Analysis and Action in Breast Cancer. In: Ceriani, R.L. (eds) Breast Cancer Immunodiagnosis and Immunotherapy. Springer, Boston, MA. https://doi.org/10.1007/978-1-4757-1296-4_11

Download citation

  • DOI: https://doi.org/10.1007/978-1-4757-1296-4_11

  • Publisher Name: Springer, Boston, MA

  • Print ISBN: 978-1-4757-1298-8

  • Online ISBN: 978-1-4757-1296-4

  • eBook Packages: Springer Book Archive

Publish with us

Policies and ethics

Search

Navigation