Sex steroid binding protein receptor (SBP-R) is related to a reduced proliferation rate in human breast cancer.

In the last years, an increasing amount of studies described a membrane receptor for the Sex Steroid Binding Protein (SBP) on several androgen-estrogen dependent tissues. One of the suggested biological roles of the interaction between SBP and its receptor seems to be a negative control of the E2 induced proliferation of human breast cancer cells through the cAMP pathway. In the present work, SBP membrane receptor was evaluated on human breast cancer specimens with a radio-binding assay. Each tissue sample was also evaluated for ER and PGR status. Cytosol Thymidine Kinase levels were measured in tissue samples in order to evaluate cell proliferation rate. SBP binding to membranes of ER +/PGR + samples was time and temperature dependent, specific and at high affinity. In addition, SBP recognized on breast cancer membranes two sites at different affinity, as previously described for other human tissues and cultured cells. Membrane SBP-R was detected in a significantly higher number of samples positive for both ER and PGR than in negative samples. SBP-R positive samples showed a significantly lower proliferation rate than SBP-R negative samples as demonstrated by TK activity. The present study contains evidences for the existence of a specific membrane receptor for SBP in breast cancer sample membranes and the presence of SBP-R seems to be strictly related to a lower proliferation rate of the sample.

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.