Plasma membrane-mediated nuclear uptake and chromatin binding of insulin in tumor cell lines

Analysis of different cellular fractions after incubation of SW 948 and SW 707 colorectal carcinoma cells or WM 266-4 melanoma cells with 125I-insulin revealed the nondegraded hormone in the chromatin of these cells. Nuclear 125I-insulin was bound to specific fragments of EcoRI-, HaeIII-, and HincII-digested chromatin. A 45-kDa chromatin protein species that binds 125I-insulin was identified. Actinomycin D and cycloheximide inhibited the insulin-stimulated expression of chromatin receptors. Uptake of 125I-insulin by isolated nuclei occurred only in the presence of plasma membranes. Thus, at least some effects of insulin on target cells can be explained by direct gene regulation instead of "second messenger" action.