Abnormal insulin-receptor down regulation and dissociation of down regulation from insulin biological action in cultured human tumor cells.

The sensitivity of insulin receptors to down regulation by insulin has been measured in cultured human tumor cells (breast tumor cell lines MCF-7, T-47D, and colon tumor cell line HCT-8). Insulin receptors on breast tumor cells were resistant to down regulation (15-17% maximum loss of insulin binding after 4 h exposure to 170 nM insulin). HCT-8 cells were sensitive to down regulation after 4 h exposure to 3.8 nM insulin, but the extent of down regulation then lessened at higher concentrations of insulin. This paradoxical behavior was associated with increasing affinity of insulin receptors for insulin following exposure to hormone. Insulin-stimulated [3H]leucine incorporation into protein was measured in parallel with studies of receptor regulation to assess the effect of preexposure of cells to insulin on cell metabolism. Maximum down regulation of receptors in all three types of tumor cell by prior exposure to insulin did not significantly alter the responsiveness of any of the cell lines to insulin. Thus insulin receptor down regulation is abnormal in these tumor lines compared with reported studies in normal cells, and this may contribute a metabolic advantage to these malignant cells over normal tissues.