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

Summary

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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Abbreviations

PBS:

phosphate-buffered saline

PM:

II-plasma membrane fraction II

Tris:

tris(hydroxymethyl)aminomethane

EDTA:

ethylendiaminetetraacetic acid

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Author information

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). https://doi.org/10.1007/BF00403363

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Key words

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