Insulin-like growth factor receptor levels are regulated by cell density and by long term estrogen deprivation in MCF7 human breast cancer cells

This work describes a reciprocal relationship between cell density and leve ls of insulin-like growth factor receptors (IGFR) in MCF7 human breast canc er cells, which adds a new dimension to the mechanism of crosstalk between estrogen and insulin-like growth factors in the regulation of breast cancer cell growth. The reduced binding of both I-125-IGF1 and alpha IR3 anti-IGF R antibody to whole cells showed that IGFR are lost from the surface of MCF 7 cells as cell density increases, and this occurred irrespective of the pr esence or absence of estradiol. Western immunoblotting further confirmed lo ss of type I IGFR from MCF7 cells with increasing cell density. Long term e strogen deprivation was found to increase the levels of IGFR at all cell de nsities, such that after 96 weeks of estrogen deprivation, IGFR levels had become similar at the highest cell density in the absence of estradiol to t he IGFR levels at the lowest cell density in the estrogen-maintained cells, and the levels of IGFR could be increased still further by estradiol. This overexpression of IGFR in the estrogen-deprived cells correlated with a re versal of response to exogenously added ligand, in that concentrations of i nsulin, IGFI, and IGFII that had stimulated growth of the estrogen-maintain ed cells became growth inhibitory to the estrogen-deprived cells. Blockade of the IGFIR with the alpha IR3 anti-IGFR antibody could partially inhibit the growth of the estrogen-deprived cells, suggesting that up-regulation of IGFR in these cells may contribute to the mechanism of adaptation to growt h in steroid-deprived conditions which results in progression to estrogen i ndependence of cell growth.