INTRACELLULAR LEVELS AND SECRETION OF INSULIN-LIKE-GROWTH-FACTOR-BINDING PROTEINS IN MCF-7/6, MCF-7/AZ AND MDA-MB-231 BREAST-CANCER CELLS - DIFFERENTIAL MODULATION BY ESTROGENS IN SERUM-FREE MEDIUM

The synthesis and secretion of insulin-like growth factor binding proteins (IGFBPs) were studied in MDA-MB-231 (estrogen-receptor-negative), MCF-7/6 (estrogen-receptor-positive, invasive) and in MCF-7/AZ (estrogen-receptor-positive, non-invasive) human breast carcinoma cell lines. Cells were grown or maintained in a chemically defined medium. Under these conditions, we found different patterns of IGFBPs in the three cell types. MDA-MB-231 cells secrete most of the IGFBPs they produce whereas MCF-7/6 and MCF-7/AZ cells maintain a high intracellular level. In MDA-MB-231 cells, the major IGFBP is IGFBP-4 which is the minor form in MCF-7/6 and MCF-7/AZ cells. IGFBP-2 and IGFBP-5 are predominant in MCF-7/6 cells while MCF-7/AZ cells produce far less IGFBPs and do not contain detectable amounts of 29-32-kDa forms (IGFBP-5). In MCF-7/6 cells, estradiol-17 beta specifically decreases both the intracellular content and secretion of IGFBP-2 and IGFBP-5. Estrogen regulation of IGFBPs cell content and secretion was found to be tamoxifen-resistant, and only slightly antagonized by ICI 182,780, a pure antiestrogen. The function of these regulations relative to the invasive phenotype and proliferation has now to be determined.