Your browser version may not work well with NCBI's Web applications. More information here...
1: Biochem Biophys Res Commun. 1997 Aug 28;237(3):690-3.
Related Articles, Links
Click here to read
Erratum in:
  • Biochem Biophys Res Commun 1997 Nov 7;240(1):246.

Insulin-like growth factor binding protein-3 induces apoptosis in MCF7 breast cancer cells.

Nickerson T, Huynh H, Pollak M.

Lady Davis Research Institute, Jewish General Hospital, Montreal, Quebec, Canada.

Insulin-like growth factors (IGFs) are known to have potent antiapoptotic activity. The antiestrogen ICI 182,780 (ICI) is a potent inhibitor of MCF7 human breast cancer cell growth and has recently been reported to act as an antiproliferative agent in part via upregulation of expression of insulin-like growth factor binding proteins (IGFBPs) -3 and -5, which attenuate the bioactivity of IGFs in many experimental systems. We show here that ICI and IGFBP-3 induce apoptosis in MCF7 cells. Treatment of MCF7 cells with 10 nM ICI or 36 nM recombinant human IGFBP. 3 for 72 hours increased apoptosis approximately 3.5-fold relative to control as quantitated by a cell death ELISA which measures DNA fragmentation. Long R3 IGF-I, an IGF-I analogue with greatly reduced affinity for IGFBPs yet similar affinity for IGF-I receptors, was a more potent inhibitor of IGFBP-3-induced and ICI-induced apoptosis than IGF-I. These results suggest that IGFBP-3 enhances apoptosis by reducing bioavailability of ligands for the IGF-I receptor and suggest that modulation of IGFBP-3 expression by ICI contributes to apoptosis induced by this compound. More generally, the data suggest that IGFBPs are regulators of apoptosis.

Publication Types:
PMID: 9299428 [PubMed - indexed for MEDLINE]