Biological relevance of the interaction between sex steroid binding protein and its specific receptor of MCF-7 cells: effect on the estradiol-induced cell proliferation.
The human breast cancer cells MCF-7 were shown to bind sex steroid binding protein (SBP) at a receptor site. The binding to whole cells was specific, time-dependent, saturable, and at high affinity. Estradiol, bound to SBP, induced a significant inhibition of SBP-cell binding at a dose of 10(-9) M. The presence of SBP, bound either to estradiol, or to cells, did not alter the amount of estradiol entering cells, but it "captured" an additional quantity of the hormone at the outer surface of cells. Furthermore, the effect of SBP on estradiol-induced MCF-7 cell proliferation was evaluated. While estradiol is an effective proliferating agent on MCF-7 cells, SBP itself did not produce any significant cell proliferation; the growth of MCF-7 cells in the presence of the complex SBP-estradiol was not different from the growth in the presence of estradiol alone; SBP bound to its receptor produced a significant reduction of the estradiol-induced cell proliferation. In summary, the present study provides evidence that the interaction of SBP with its receptor on MCF-7 cells is not involved in the uptake of estradiol, but it can modify the effect of estradiol at target site by a mechanism which is not likely to be a simple sequestration of the hormone at the outer surface of cells.
Dipartimento di Fisiopatologia Clinica, Università di Torino, Italy.
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Fortunati
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Fissore
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Fazzari
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Berta
E
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Benedusi-Pagliano
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Frairia
D001943:Breast Neoplasms / Q000378:metabolism* / Q000473:pathology; D002455:Cell Division / Q000187:drug effects; D003470:Culture Media; D004054:Diethylstilbestrol / Q000494:pharmacology; D004958:Estradiol / Q000378:metabolism / Q000494:pharmacology*; D006801:Humans; D011956:Receptors, Cell Surface / Q000378:metabolism*; D012738:Sex Hormone-Binding Globulin / Q000378:metabolism*; D014407:Tumor Cells, Cultured
D003470:Culture Media; D011956:Receptors, Cell Surface; D012738:Sex Hormone-Binding Globulin; C063572:sex hormone-binding globulin receptor; D004958:Estradiol; D004054:Diethylstilbestrol