The Japanese journal of surgery

, Volume 17, Issue 5, pp 369–376 | Cite as

Analysis of estrogen receptors in human breast cancer by assays using monoclonal antibodies and by the dextran-coated charcoal method

  • Noboru Fujino
  • Kiyoshi Sakamoto
  • Nobuyuki Shigaki
  • Jun-ichi Yamashita
  • Masaharu Kimura
  • Masanobu Akagi
Original Articles
  • 17 Downloads

Abstract

Estrogen receptors (ER) were analyzed in 63 human breast cancers by immunocytochemical assay, and by enzyme-immunoassay, using monoclonal antibodies against human ER protein, and also by the dextrancoated characoal method. The specific staining was observed only in the nucleus of cancer cells by the immunocytochemical assay, and the presence of nuclear staining by this assay was closely associated with the estimation of the cytosolic ER content by both the dextran-coated charcoal method and the enzyme-immunoassay. In the latter, the cytosolic ER content corres-pondingly increased with the nuclear ER content. Both the cytosolic and nuclear ER contents correlated well with those obtained by the dextrancoated charcoal method. Furthermore, the cytosolic ER contents obtained by the enzyme-immunoassay and the dextran-coated charcoal method correlated significantly with the age of the patient, but not with the nuclear ER contents. These above mentioned results suggest that ER is present mainly in the nucleus of breast cancer cells and that the cytosolic ER obtained by these two assays is the unoccupied one released from the nucleus.

Key Words

human breast cancer estrogen receptor enzyme-immuno-assay immunocytochemical assay dextran-coated charcoal method 

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References

  1. 1.
    Nomura, Y, Kobayashi S, Takatani O, Sugano H, Matsumoto K, McGuire WL. Estrogen receptor and endocrine responsiveness in Japanese versus American breast cancer. Cancer Res 1977; 37; 106–110.PubMedGoogle Scholar
  2. 2.
    Osbome CK, Yochimowitz MG, Knight WA, McGuire WL. The value of estrogen and progesterone receptors in the treatment of breast cancer. Cancer (Phila) 1980; 46: 2884–2888.CrossRefGoogle Scholar
  3. 3.
    Jensen EV. Hormone dependency of breast cancer. Cancer 1981; 47: 2319–2326.PubMedCrossRefGoogle Scholar
  4. 4.
    Romic-Stojkovic R, Gamulin S. Relationship of cytoplasmic and nuclear estrogen receptors and progesterone receptors in human breast cancer. Cancer Res 1980; 40: 4821–4825.PubMedGoogle Scholar
  5. 5.
    Nishimura R, Kimura M, Tokunaga T, Akagi M. Measurement of nuclear estrogen receptors by charcoal absorption: relationships of cytoplasmic and nuclear estrogen receptors and progesterone receptors in human breast cancer. Gann 1982; 73: 713–720.PubMedGoogle Scholar
  6. 6.
    Barnes DM, Skinner LG, Ribeiro GG. Triple hormone receptor assay: A more accurate predictive tool for the treatment of advanced breast cancer. Br J Cancer 1979; 40: 862–865.PubMedGoogle Scholar
  7. 7.
    Coffer AI, Lewis KM, Brockas AJ, King RJB. Monoclonal antibodies against a component related to soluble estrogen receptor. Cancer Res 1985; 45: 3686–3693.PubMedGoogle Scholar
  8. 8.
    Greene GL, Nolan C, Engler JP, Jensen EV. Monoclonal antibodies to human estrogen receptor. Proc Natl Acad Sci 1980; 77: 5115–5119.PubMedCrossRefGoogle Scholar
  9. 9.
    Raam S, Nemeth E, Tamura H, O'Briain DS, Cohen JL. Immunohistochemical localization of estrogen receptors in human mammary carcinoma using antibodies to the receptor protein. Eur J Cancer Clin Oncol 1982; 18: 12.CrossRefGoogle Scholar
  10. 10.
    Coffer AI, Spiller GH, Lewis KM, King RJB. Immunoradiometric studies with monoclonal antibody against a component related to human estrogen receptor. Cancer Res 1985; 45: 3694–3698.PubMedGoogle Scholar
  11. 11.
    Greene GL, and Jensen EV. Monoclonal antibodies of probes for estrogen receptor detection and characterization. J Steroid Biochem 1982; 16: 353–359.PubMedCrossRefGoogle Scholar
  12. 12.
    King RJ, Coffer AI, Gilbert J, Lewis K, Nash R, Millis R, Raju S, Taylor RW. Histochemical studies with a monoclonal antibody raised against a partially purified soluble estradiol receptor preparation from human myometrium. Cancer Res 1985; 45: 5728–5730.PubMedGoogle Scholar
  13. 13.
    King WJ, Desombre ER, Jensen EV, Greene GL. Comparison of immunocytochemical and steroid-binding assays for estrogen receptor in human breast tumors. Cancer Res 1985; 45: 293–304.PubMedGoogle Scholar
  14. 14.
    McCleelan MC, West NB, Tacha DE, Greene GL, Brenner RM. Immunocytochemical localization of estrogen receptors in macaque reproductive tract with monoclonal antiestrophilins. Endocrinology 1984; 114: 2002–2014.Google Scholar
  15. 15.
    King WJ, Greene GL. Monoclonal antibodies localize oestrogen receptor in the nuclei of target cells. Nature 1984; 307: 745–747.PubMedCrossRefGoogle Scholar
  16. 16.
    Toi M, Hamada Y, Seto Y, Hisamatsu K, Suehiro S, Niimoto M, Hattori T. Estrogen receptor assay of breast cancer by an immunoenzymatic staining with monoclonal antibody. Igaku-no-ayumi 1986; 136: 227–228. (in Japanese)Google Scholar
  17. 17.
    Pertschuk LP, Eisenberg KB, Carter AC, Feldman JG. Immunohistologic localization of estrogen receptors in breast cancer with monoclonal antibodies. Correlation with biochemistry and clinical response. Cancer 1985; 55: 1513–1518.PubMedCrossRefGoogle Scholar
  18. 18.
    Japan Mammary Cancer Society, General Rules for Clinical and Pathological Record of Mammary Cancer 5th Edition, Tokyo: Kanehara, 1979; 23–41.Google Scholar
  19. 19.
    Lowry OH, Rosebrough NJ, Farr AL, Randall RJ. Protein measurement with the folin reagent. J Biol Chem 1951; 193: 265–275.PubMedGoogle Scholar
  20. 20.
    Matsumoto K, Ochi H, Nomura Y, Takatani O, Izuo M, Okamoto R, Sugano H. Progesterone and estrogen receptors in Japanese breast cancer. In: W.L. McGuire ed. Hormone Receptors and Breast Cancer. New York, Raven Press 1978; 43–58.Google Scholar
  21. 21.
    Scatchard G The attraction of proteins for small molecules and ions. Ann NY Acad Sci 1949; 51: 660–672.Google Scholar
  22. 22.
    Stancel GM, Leung KMT, Gorski J. Estrogen receptors in the rat uterus. Multiple forms produced by concentration-dependent aggregation. Biochemistry 1973; 12: 2130–2136.PubMedCrossRefGoogle Scholar
  23. 23.
    Notides AC, Nielsen S. The molecular mechanism of thein vitro 4s to 5s transformation of the uterine estrogen receptor. J Biol Chem 1974; 249: 1866–1873.PubMedGoogle Scholar
  24. 24.
    Jensen EV, DeSombre ER. Estrogen-receptor interaction. Science 1973; 182: 126–134.PubMedGoogle Scholar
  25. 25.
    Leake R. Current views on estrogen receptors. TIBS, June 1976; 137–139.Google Scholar
  26. 26.
    Welshons WV, Lieberman ME, Gorski J. Nuclear localization of unoccupied oestrogen receptors. Nature 1984; 307: 747–749.PubMedCrossRefGoogle Scholar
  27. 27.
    Martin PM, Sheridan PJ. Toward a new model for the mechanism of action of steroids. J Steroid Biochem 1982; 16: 215–229.PubMedCrossRefGoogle Scholar
  28. 28.
    Martin PM, Magdelenat HP, Benyahia B, Rigand O, Katzenellenbogen JA. New approach for visualizing estrogen receptors in target cells using inherently fluorescent ligands image intensification. Cancer Res 1983; 43: 4956–4965.PubMedGoogle Scholar
  29. 29.
    MacFarlane JK, Fleiszer D, Fazekas AG. Studies on estrogen receptors and regression in human breast cancer. Cancer 1980; 45: 2998–3003.PubMedCrossRefGoogle Scholar
  30. 30.
    Kimura M, Nishimura R, Akagi M. Studies on the mechanism of estrogen action in human breast cancer. Jap J Cancer Clin 1985; 31: 263–267.Google Scholar
  31. 31.
    Yamamoto KR, Alberts B.In vitro conversion of estradiol-receptor protein to its nuclear form: dependence on hormone and DNA. Proc Nat Acad Sci 1972; 69: 2105–2109.PubMedCrossRefGoogle Scholar
  32. 32.
    Lawson DEM, Wilson PW. Intranuclear localization and receptor protein for 1,25-dihydroxycholecalciferol in chick intestine. Biochem J 1974; 144: 573–583.PubMedGoogle Scholar
  33. 33.
    Spindler BJ, MacLeod KM, Ring J, Baxter JD. Thyroid hormone receptors. J Biol Chem 1975; 250: 4113–4119.PubMedGoogle Scholar
  34. 34.
    Walters MR, Hunziker W, Norman AW. Unoccupied 1,25-hydroxy vitamin D3 receptors. J Biol Chem 1980; 255: 6799–6805.PubMedGoogle Scholar
  35. 35.
    Peck EJ, Clark JH. Effect of ionic strength on charcoal adsorption assays of receptor-estradiol complexes. Endocrinology 1977; 101: 1034–1043.PubMedCrossRefGoogle Scholar
  36. 36.
    Rosen PP, Menendez-Botet CJ, Nisselbaum JS, Urban JA, MiKe V, Fracchia A, Schwartz MK. Pathological review of breast lesions analyzed for estrogen receptor protein. Cancer Res 1975; 35: 3187–3194.PubMedGoogle Scholar
  37. 37.
    Antoniades K, Spector H. Correlation of estrogen receptor levels with histology and cytomorphology in human cancer. J Clin Pathol 1979; 71: 497–503.Google Scholar
  38. 38.
    DeSombre ER, Jensen EV. Estrophilin assays in breast cancer: quantitative features and application to the mastectomy specimen. Cancer 1980; 46: 2783–2790.PubMedCrossRefGoogle Scholar
  39. 39.
    Jensen, EV, Greene GL, Closs LE, DeSombre ER, Nadzi M. Receptors reconsidered: a 20-year perspective. Recent Prog Horm Res 1982; 38: 1–40.PubMedGoogle Scholar

Copyright information

© The Japan Surgical Society 1987

Authors and Affiliations

  • Noboru Fujino
    • 1
  • Kiyoshi Sakamoto
    • 1
  • Nobuyuki Shigaki
    • 1
  • Jun-ichi Yamashita
    • 1
  • Masaharu Kimura
    • 1
  • Masanobu Akagi
    • 1
  1. 1.Second Department of SurgeryKumamoto University Medical SchoolKumamotoJapan

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