PARADOXICAL BIOLOGICAL EFFECTS OF OVEREXPRESSED INSULIN-LIKE GROWTH FACTOR-I RECEPTORS IN CHINESE-HAMSTER OVARY CELLS

One major approach to the study of growth factor receptor action has been to overexpress wild-type or mutant receptors in cultured cells and to evaluate biological responses to exogenous ligand. Studies of this type with insulin and insulin-like growth factor-I (IGF-I) receptors often use Chinese hamster ovary (CHO) cells. We have compared the effect of receptor overexpression in CHO cells and in NIH-3T3 fibroblasts in order to assess the suitability of CHO cells for studies of this nature and the contribution of cell type-specific factors to those responses generally assayed. Overexpression of IGF-I receptors in NIH-3T3 cells resulted in increased sensitivity and maximal responsiveness of thymidine incorporation, 2-deoxyglucose uptake, and phosphatidylinositol-3 (PI3) kinase activation to IGF-I stimulation. In CHO cells, on the other hand, overexpression of either IGF-I or insulin receptors increased the sensitivity of thymidine incorporation to ligand, but maximal responsiveness was unchanged or decreased. Overexpression of the insulin receptor increased sensitivity of glucose uptake and the maximal response of PI3 kinase activation to insulin. Overexpression of the IGF-I receptor did not affect sensitivity or maximal responsiveness of glucose uptake or PI3 kinase activation to IGF-I. These data suggest that IGF-I and insulin signal pathways may differ in CHO cells, and that there may even be divergent IGF-I signaling pathways for short vs. long-term effects. Whether this is a result of differences in the number of endogenous receptors, hybrid receptor formation, or defects in post-receptor signaling, the use of CHO cells to assess receptor function must be approached with caution. (C) 1993 Wiley-Liss, Inc.