The overexpression of insulin receptor makes CHO cells resistant to the action of IGF-1: role of IRS-1.
We investigated the influence of the relative abundance of insulin and IGF-1 receptors on cellular growth, by measuring the stimulation of c-fos expression and of H3-thymidine incorporation into DNA by insulin and IGF-1 in CHO cells overexpressing insulin Receptor (CHO-IR). We found that CHO-IR cells were resistant to the action of IGF-1, but were more responsive to insulin, compared to parental clone. This result suggest the presence of a limiting step, distal to the IGF-1 receptor, in the transduction pathway. To address this question we measured the IGF-1 effect on c-fos expression in CHO-IR cells, transiently transfected with the cDNA for IRS-1, the common intracellular substrate for both insulin and IGF-1 receptors (CHO-IR/IRS-1 cells). In these cells IGF-1 stimulated a 10 fold higher c-fos expression compared to CHO-IR cells. These results suggest that the abundance of IRS-1, relative to the number of insulin and IGF-1 receptors, represents a limiting step for the intracellular transduction of insulin and IGF-1 biological messages.
Maggi
D
D
Department of Endocrinology and Metabolism (Di.S.E.M.), University of Genova, Italy.
Laurino
C
C
Andraghetti
G
G
Cordera
R
R
D000818:Animals; D001483:Base Sequence; D016466:CHO Cells; D002455:Cell Division / Q000187:drug effects; D006224:Cricetinae; D017931:DNA Primers; D018076:DNA, Complementary; D016762:Genes, fos; D007328:Insulin / Q000494:pharmacology; D055504:Insulin Receptor Substrate Proteins; D007334:Insulin-Like Growth Factor I / Q000494:pharmacology*; D008969:Molecular Sequence Data; D010750:Phosphoproteins / Q000502:physiology*; D011972:Receptor, Insulin / Q000378:metabolism*; D015398:Signal Transduction
D017931:DNA Primers; D018076:DNA, Complementary; D007328:Insulin; D055504:Insulin Receptor Substrate Proteins; D010750:Phosphoproteins; D007334:Insulin-Like Growth Factor I; D011972:Receptor, Insulin