Effects of Insulin-Like Growth Factors (IGFs) and IGF Receptor Antibodies on the Proliferation of Human Breast Cancer Cells
作者:
De LeonD. D.,
WilsonD. M.,
PowersM.,
RosenfeldR. G.,
期刊:
Growth Factors
(Taylor Available online 1992)
卷期:
Volume 6,
issue 4
页码: 327-336
ISSN:0897-7194
年代: 1992
DOI:10.3109/08977199209021544
出版商: Taylor&Francis
关键词: breast cancer;Insulin-like growth factors;MCF-7
数据来源: Taylor
摘要:
AbstractIt has been shown previously that MCF-7 cells proliferate in response to nanomolar concentrations of IGF-I and IGF-II. It has also been reported that the actions of both peptides are mediated through the IGF-I receptor. To further characterize these observations, we used MCF-7 and Hs578T cell lines in the serum-free/phenol red-free system developed by Ogasawara and Sibarsku, 1988. Cell proliferation was studied in the presence of insulin, IGF-I and-II and a series of growth factor receptor antibodies. No effect was observed on Hs578T cell proliferation with any of the growth factors. However, MCF-7 cells were stimulated 4-5 fold with IGF-I and insulin, while IGF-II was only slightly less potent.αIR3, a monoclonal antibody directed against the IGF-I receptor, was stimulatory when added alone. However,αIR3 blocked approximately 50% of the IGF-I response, only 5% of the insulin response, and did not block the IGF-II effect on cell proliferation. These data suggest thatαIR3 and IGF-I are acting as agonists through the IGF-I receptor, but that insulin and IGF-II are acting through other receptors. Two different IGF-II/M-6-P receptor antibodies and an insulin receptor antibody failed to significantly block IGF-II actions. All three antibodies were stimulatory when added alone.β-gal inhibited 27% of the IGF-II response and had no effect when added alone. Sinceβ-gal decreases the binding affinity of the IGF-II/M-6-P receptor for IGF-II and does not bind to the IGF-I or insulin receptor, these data suggest the possibility that IGF-II mitogenic action is mediated through the IGF-II/M-6-P receptor. In summary, these data indicate that nanomolar concentration of insulin, IGF-I and IGF-II are potent mitogens in MCF-7 cells and can potencially stimulate cell proliferation through all three receptors.
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