Previous studies have shown that the nontransformed AKR-2B cells when arrested in the G1 phase of the cell cycle due to low-molecular-weight nutrient (amino acid) deficiency exhibit a 5- to 10-fold lower level of epidermal growth factor (EGF) receptor activity than do the same cells in the rapidly growing state or arrested in G1 due to growth factor deficiency. The chemically transformed AKR-MCA and C3H/MCA-58 cell lines spontaneously arrest growth in G1 due to nutrient deficiency when grown to saturation density in medium with 10% fetal bovine serum. An examination of 125I-labeled EGF binding in rapidly growing and G1-arrested AKR-MCA and C3H/MCA-58 cells showed that the G1-arrested chemically transformed cells also have a 10- to 20-fold reduction in the amount of 125I-labeled EGF binding relative to the same cells in the rapidly growing state. Stimulation of DNA synthesis in the arrested cells by the addition of serum-free medium caused a 6- to 10-fold increase in 125I-labeled EGF binding. This recovery of receptor activity was inhibited by actinomycin D and cycloheximide, suggesting that new messenger RNA synthesis as well as increased protein synthesis is necessary for the recovery of EGF binding. A comparison of EGF binding in C3H/MCA-58 cells and the nontransformed parent line (C3H/10T½) in the rapidly growing state showed the same approximate level of receptor activity. However, the rapidly growing AKR-MCA cells had approximately one-tenth the amount of EGF binding as did the rapidly growing nontransformed parent line (AKR-2B). Scatchard analysis of binding data showed a 10-fold greater number of receptors in the AKR-2B cells relative to the AKR-MCA cells with a lesser difference in apparent receptor affinity. The chemically transformed BP-3T3, like the other two chemically transformed lines, was also demonstrated to arrest growth spontaneously due to nutrient deficiency with an associated 100-fold decrease in EGF binding. Rapidly growing BP-3T3 cells had only slightly less 125I-labeled EGF binding than did the nontransformed parent line (BALB-3T3) in the rapidly growing state. The data indicate that one mechanism for reduction of EGF binding in chemically transformed cells is the propensity of these cells to arrest growth in G1 at saturation density due to low-molecular-weight nutrient deficiency, a state associated with decreased EGF binding.


Supported by USPHS Grant CA 27217 awarded by the National Cancer Institute, Department of Health and Human Services.

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