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Differential IGF‐independent effects of insulin‐like growth factor binding proteins (1–6) on apoptosis of breast epithelial cells
Author(s) -
Perks Claire M.,
Bowen Samantha,
Gill Zahidah P.,
Newcomb Paul V.,
Holly Jeff M.P.
Publication year - 1999
Publication title -
journal of cellular biochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.028
H-Index - 165
eISSN - 1097-4644
pISSN - 0730-2312
DOI - 10.1002/(sici)1097-4644(19991215)75:4<652::aid-jcb11>3.0.co;2-0
Subject(s) - apoptosis , ceramide , insulin like growth factor binding protein , growth factor , flow cytometry , biology , binding protein , programmed cell death , growth inhibition , cell growth , microbiology and biotechnology , endocrinology , medicine , insulin like growth factor , receptor , biochemistry , gene
We have demonstrated previously that insulin‐like growth factor binding protein (IGFBP)‐3 alone has little growth inhibitory effect on Hs578T human breast cancer cells, but that it can dramatically accentuate the apoptotic response to the physiological trigger, ceramide, in an IGF‐independent manner. We have now studied the potential of other IGFBPs (1–6) to interact with apoptotic signalling pathways. Hs578T cells were preincubated with a binding protein (100 ng/ml) for 24 h, followed by co‐incubation of the binding protein with an apoptotic dose of ceramide or RGD‐containing peptide for a further 24 h. Apoptosis was assessed using flow cytometry, MTT (3‐[4,5‐Dimethylthiazol‐2‐yl]‐2,5‐diphenyltetrazolium bromide; thiazolyl blue) assay and morphological assessment. Binding protein profiles were determined using ligand and immunoblotting techniques. Each of the IGFBPs (1–6) alone had no significant ( P > 0.05) growth inhibitory effects relative to control cells. In contrast to IGFBP‐3, which significantly ( P < 0.05) accentuated C2‐induced apoptosis, IGFBP‐1, ‐2, and ‐6 had no effect, whereas IGFBP‐4 and ‐5 each caused marked ( P < 0.01) inhibition of ceramide‐induced programmed cell death. Apoptosis induced by RGD was also significantly ( P < 0.05) reduced by IGFBP‐5, whereas IGFBP‐3 had no effect. These data provide evidence to suggest that individual IGFBPs have specific IGF‐independent effects and act differentially on apoptotic signalling pathways. J. Cell. Biochem. 75:652–664, 1999. © 1999 Wiley‐Liss, Inc.