Premium
Recombinant insulin‐like growth factor binding protein‐1 inhibits IGF‐I, serum, and estrogen‐dependent growth of MCF‐7 human breast cancer cells
Author(s) -
Figueroa José A.,
Sharma Jivesh,
Jackson James G.,
McDermott Martin J.,
Hilsenbeck Susan G.,
Yee Douglas
Publication year - 1993
Publication title -
journal of cellular physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.529
H-Index - 174
eISSN - 1097-4652
pISSN - 0021-9541
DOI - 10.1002/jcp.1041570204
Subject(s) - mcf 7 , human breast , insulin like growth factor binding protein , insulin like growth factor , recombinant dna , estrogen , growth factor , endocrinology , breast cancer , medicine , cancer , cancer research , binding protein , biology , chemistry , biochemistry , receptor , gene
The insulin‐like growth factors (IGFs) are potent mitogens for breast cancer cells and their activity is modulated by high affinity binding proteins (IGFBPs). We have recently shown that IGFBP‐1 purified from human amniotic fluid neutralizes IGF‐I‐dependent growth of MCF‐7 cells. In this study we examined the effects of recombinant IGFBP‐1 (rBP‐1) on IGF‐I, estradiol (E 2 ), and serum‐induced monolayer and anchorage independent growth (AIG) of MCF‐7 cells. Under serum‐free conditions, rBP‐1 had no effect on MCF‐7 basal monolayer growth. However, 40 nM rBP‐1 completely blocked the mitogenic action of both IGF‐I and 5% charcoal stripped serum (CSS). This concentration of rBP‐1 partially inhibited E 2 ‐induced growth, while 80 nM rBP‐1 completely abolished E 2 mitogenicity. The addition of either excess IGF‐I or 5 nM [Arg 3 ]IGF‐I, a species that does not bind IGFBPs, neutralized rBP‐1 inhibitory effects. In AIG assays, 80 nM rBP‐1 reduced colony number by at least 70% and decreased colony size in all treatment groups compared to control. We examined rBP‐1 effects on both IGF‐I binding to MCF‐7 membranes and activation of type I IGF receptor (IGFR 1 ) and found that 80 nM rBP‐1 reduced IGF‐I receptor binding to levels of nonspecific binding and completely abolished ligand‐dependent IGFR, phosphorylation. However, neither treatment with 5% CSS nor exposure to E 2 resulted in IGFR 1 phosphorylation suggesting that different mechanism(s) are responsible for rBP‐1 inhibitory action under this condition. Our data suggest rBP‐1 may serve as an antagonist of human breast cancer growth by interfering with growth factor‐mediated cell proliferation. © 1993 Wiley‐Liss, Inc.