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 bin ding 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 i t ''captured'' an additional quantity of the hormone at the outer surf ace of cells. Furthermore, the effect of SBP on estradiol-induced MCF- 7 cell proliferation was evaluated. While estradiol is an effective pr oliferating agent on MCF-7 cells, SBP itself did not produce any signi ficant cell proliferation; the growth of MCF-7 cells in the presence o f the complex SBP-estradiol was not different from the growth in the p resence of estradiol alone; SBP bound to its receptor produced a signi ficant reduction of the estradiol-induced cell proliferation. In summa ry, the present study provides evidence that the interaction of SBP wi th its receptor on MCF-7 cells is not involved in the uptake of estrad iol, but it can modify the effect of estradiol at target site by a mec hanism which is not likely to be a simple sequestration of the hormone at the outer surface of cells.