PERTURBATION BY INSULIN OF HUMAN-BREAST CANCER CELL-CYCLE KINETICS

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  • 1 January 1984
    • journal article
    • research article
    • Vol. 44  (8) , 3570-3575
Abstract
The growth of cultured human breast cancer cell is sensitive to physiological concentrations of insulin, suggesting that it may regulate breast cancer growth in vivo. The mechanisms for the growth effects of insulin are poorly defined. The effects of insulin on the cell cycle kinetics of asynchronous MCF-7 human breast cancer cells were examined growing in serum-free medium. When the [3H]thymidine labeling index was used to estimate the S-phase fraction, insulin added to asynchronously growing cells resulted in a time-dependent increase in the proportion of cells engaged in DNA synthesis. Computer analysis of DNA histograms obtained by flow cytometry of mithramycin-stained cells also shows a time-dependent progression of cells into and through the S-phase compartment. Adding insulin to asynchronous cells after 16 h, 66% of cells are in S-phase compared to 37% in controls. The effect of insulin on the cell cycle progression of MCF-7 cells is also dose dependent. Stimulation is observed with physiological insulin concentrations of 0.1-1.0 nM; maximal effects are observed with 1.0-10 nM insulin. Various insulin analogues enhance the progression of cells into S phase, in proportion to their ability to bind to the insulin receptor in MCF-7 cells (porcine .gtoreq. chicken > guinea pig > deoctapeptide insulin), while unrelated peptide hormones have no effect on the cell cycle kinetics. Cell cycle analysis, after the addition of colchicine to prevent mitosis and the reentry of cells into G1, demonstrates a shortened G1 in response to insulin. Continuous [3H]thymidine-labeling studies, after the addition of colchicine, suggest that the growth fraction is .apprx. 88% with or without insulin. Insulin causes a marked perturbation of the cell cycle kinetics of MCF-7 human breast cancer cells by facilitating the transit of cells through G1. This effect is apparently mediated via the insulin receptor.