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Plasma membrane-integrated estrogen receptors in breast tissue: Possible modulator molecules for intracellular hormone level


Plasma membrane fractions from tumor specimens of 14 peri-and postmenopausal primary breast cancer patients and from non-neoplastic tissues were prepared by sucrose density sedimentation The membranes were desintegrated by Triton X-100 and the 3H-estrogen binding capacity of membrane-derived proteins was determined. The receptor system found in the plasma membranes was mainly of low affinity and high capacity, working apparently in tandem with the high affinity and low capacity system described for the cytosol. Receptor concentrations in plasma membranes of non-neoplastic and neoplastic tissue were distributed over a wide range of values, but a significantly lowered receptor capacity was found in neoplastic tissue. An association constant, Ka=6.35·1010 M -1 was determined for neoplasma-derived membrane receptor proteins, whereas non-neoplastic tissue membrane proteins were not saturable, when incubated with up to 150 pmol 3H-estradiol. From a Scatchard plot analysis of some experiments a molar concentration of binding sites for membrane proteins, derived from breast cancer tissue, n(M)=1.7·10-12/mg protein was extrapolated. Furthermore, ample evidence was provided by an estrogen fluorescence probe that an estrogen binding system is located within the plasma membrane. It is suggested that the estrogen binding capacity of the epithelium cell membrane, due to the phospholipid moiety, can modulate the estrogen uptake and, thus, preventing hazardous high levels of estrogens within the cytoplasm. The presented experimental data throw a new light on the use of antiestrogens in the treatment of breast cancer.

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  1. Beatson GT (1898) On the treatment of inoperable cases of carcinoma of the mamma: Suggestions for a new method of treatment with illustrative cases. Lancet II:104–107:162–165

  2. Bennett DC (1980) Morphogenesis of branching tubules in cultures of cloned mammary epithelial cells. Nature 285:657–659

  3. Bickoff EM, Spencer RR, Witt SC, Kuckles BE (1969) Studies on the chemical and biological properties of coumestrol and related compounds. Technical Bulletin No 1408 Agricultural Research Service, Department of Agriculture, Washington DC

  4. Brewin TB (1974) Oral communication at the 8th Int. Congress of Chemotherapy, Athens

  5. Burton K (1956) A study of the conditions and mechanism of the diphenylamine reaction for the colorimetric estimation of deoxyribonucleic acid. Biochem J 62:315–323

  6. Cole MP, Jones CTA, Todd IDH (1972) The treatment of advanced carcinoma of the breast with the antiestrogenic agent tamoxifen (ICI 46, 474) — a series of 96 patients. Adv Antimicro Antineoplastic Chemother 2:529–531

  7. Erdos T, Bessada R, Fries J (1969) Binding of oestradiol to receptor substances present in extracts from calf uterus. FEBS Lett 5:161–164

  8. Herzt R (1973) The estrogen-cancer hypothesis with special emphasis on DES. In: Hiatt HH, Watson JD, Winston JA (eds) Origins of human cancer, Book C, Human risk assessment. Cold Spring Harbor Conferences on Cell Proliferation, pp 1665–1673

  9. Jackson RJ, Stewart HB, Sachs G (1977) Isolation and purification of normal and malignant colonic plasma membranes. Cancer 40:2487–2496

  10. Jungblut PW, Games J, Hughes A, Kallweit E Sierralta W, Szendro P, Wagner K (1976) Activation of transcription-regulating proteins by steroids. J Steroid Biochem 7:1109–1116

  11. Korenman SG (1980) Estrogen window hypothesis of the etiology of breast cancer. Lancet I:700–701

  12. Kreitmann B, Derache B, Bayard F (1978) Measurement of the corticosteroid-binding globulin, progesterone, and progesterone “receptor” content in human endometrium. J Clin Endocrinol Metab 47:350–353

  13. Leclercq G, Henson JC, Doboel MC, Mattheiem WH (1975) Estrogen receptors in breast cancer: A changing concept. Br Med J 1:185–189

  14. Lee SH: (1977) Cytochemical study of estrogen receptor in human mammary cancer. Am J Clin Pathol 70:197–203

  15. Lee SH (1979) Cancer cell estrogen receptor of human mammary carcinoma. Cancer 44:1–12

  16. Lee SH (1980) Cellular estrogen and progesterone receptors in mammary carcinoma. Am J Clin Pathol 73:323–329

  17. Lowry OH, Rosebrough NJ, Farr AL, Randall RJ (1951) Protein measurement with the folin phenol reagent. J Biol Chem 193:265–275

  18. MacMahon B, Cole P, Brown J (1973) Etiology of human breast cancer: A review. J Natl Cancer Inst 50:21–43

  19. Milgrom E, Atger M, Baulieu EE (1973) Studies on estrogen entry into uterine cells and on estradiolreceptor complex attachment to the nucleus-Is the entry of estrogen into uterine cells a proteinmediated process? BBA 320:267–271

  20. Müller RE, Wotiz HH (1979) Kinetics of estradiol entry into unterine cells. Endocrinology 105:1107–1114

  21. NIH Consensus Development Conference (1979) Steroid receptors in breast cancer NIH, June 27–29, Vol 2, No 6

  22. Nicholson RJ, Golder MP, Davies, P, Griffiths K (1976) Effects of estradiol-β and tamoxifen on total and accessible cytoplasmic estradiol-β 17 receptors in DMBA-induced rat mammary tumors. Eur J Cancer 12:711–717

  23. Peck Jr EJ, Burgner J, Clark JH (1973) Estrophilic binding sites of the uterus. Relation to uptake and retention of estradiol in vitro. Biochemistry 12:4596–4603

  24. Pietras RJ, Szego CM (1977) Specific binding sites for oestrogen at the outer surface of isolated endometrial cells. Nature 265:69–72

  25. Rochefort H, André J, Baskervitch PP, Kallos J, Vignon F, Westley B (1980) Nuclear translocation and interactions of the estrogen receptor in uterus and mammary tumors. J Steroid Biochem 12:135–142

  26. Sebesteny A, Taylor-Papadimitrious J, Ceriani R, Millis R, Schmitt Ch, Trevan D (1979) Primary human breast carcinomas transplantable in the nude mouse. J Natl Cancer Inst 63:1331–1337

  27. Segi M, Kurihara M, Matsuyama T (1969) Cancer mortality for steroid sites in 24 countries. Sendai: Tohoku University School of Medicine 5:1964–1965

  28. Sheridan PJ, Buchanan JM, Anselmo VC, Martin PM (1979) Equilibrium: The intracellular distribution of steroid receptors. Nature 282:579–582

  29. Skinner L (1979) Data presented at the NIH Consensus Development Conference. Steroid receptors in breast cancer. NIH, June 27–29

  30. Spang-Thomson MS (1976) Heterotransplantation of a human mammary carcinoma to the mouse mutant nude. Acta Pathol Microbiol Scand [A] 84:350–352

  31. Suyemitsu T, Terayama H (1975) Specific binding sites for natural glucocorticoids in plasma membranes of rat liver. Endocrinology 96:1499–1508

  32. Tagnon HJ (1977) Antiestrogens in treatment of breast cancer. Cancer 39:2956–2964

  33. Thorson T (1980) Occupied, and unoccupied estradiol receptor in human breast tumor cytosol. J Steroid Biochem 13:405–408

  34. Torriani A (1968) In: Colwick SP, Kaplan NO (eds) Methods in enzymology. Academic Press, New York, pp 212–215

  35. Walker R, Cove DH, Howell A (1980) Histological detection of estrogen receptor in human breast carcinoma. Lancet I:171–173

  36. Ward HWC (1974) Antiestrogens in treatment of breast cancer. Br Med J 2:500

  37. Zänker KS, Prokscha GW, Blümel G (1980) Modulation of estrogen receptor capacity by phosphatidyl choline. J Clin Chem Clin Biochem 18:728

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Correspondence to K. S. Zänker.

Additional information

Shortly after accepting this manuscript for publication a review was published in: Anticancer Res 1: 39–44 (1981) by Barnett Zummoff on the role of, estrogen excess in human breast cancer. This article is within the scope of the present paper and should be noticed by the reader

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Zänker, K.S., Prokscha, G.W. & Blümel, G. Plasma membrane-integrated estrogen receptors in breast tissue: Possible modulator molecules for intracellular hormone level. J Cancer Res Clin Oncol 100, 135–148 (1981).

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Key words

  • Estrogen receptor
  • Breast cancer tissue
  • Plasma membrane
  • fluorescence probe
  • Antiestrogen