Estrogen and Insulin Modulation of Intracellular Insulin-like Growth Factor Binding Proteins in Human Breast Cancer Cells: Possible Involvement in Lysosomal Hydrolases Oversecretion

Abstract

Differences in insulin-like growth factor binding proteins (IGFBPs) expressed within estrogen receptor positive (ER+, MCF-7/6) and negative (ER−, MDA-MB-231) human breast cancer cells cultured in chemically defined medium were observed. In the absence of insulin, 17 β-estradiol affects this expression in ER+ cells by significantly reducing 34 and 28 kDa species. In ER+ cells, insulin appears to minimize the estrogen induced reduction of these 34 and 28 kDa IGFBPs and stimulates a 24 kDa type. We suggest that through its association with a given IGFBP, insulin-like growth factor-II (IGF-II) directs lysosomal enzymes to secretion by its binding to the mannose-6-phosphate/IGF-II receptors present in the Golgi apparatus. Alternatively, the association of IGF-II with another IGFBP would inhibit this binding and lead to its autocrine or intracrine mitogenic action via the IGF-I receptor.