RECEPTOR-BINDING AND GROWTH-PROMOTING ACTIVITY OF INSULIN-LIKE GROWTH-FACTORS IN HUMAN-BREAST CANCER-CELLS (T-47D) IN CULTURE

  • 1 January 1984
    • journal article
    • research article
    • Vol. 44  (12) , 5486-5490
Abstract
Insulin-like growth factors (IGF) and insulin are known to be mitogenic to a variety of cell types, although a growth-regulatory role of IGF on human breast cancer cells has not yet been fully investigated. The receptor binding and the effect on growth of IGF and insulin was examined in a human breast cancer cell line (T-47D). Specific binding of 125I-basic somatomedin (BSM/IGF-I), 125I-multiplication-stimulating activity (MSA III-2/IGF-II) and 125I-insulin was demonstrated in monolayer T-47D cells grown on plastic substratum. When the binding of 125I-BSM and 125I-MSA III-2 was studied, unlabeled BSM and unlabeled MSA were the most effective competitors for the respective binding sites. Unlabeled insulin at high concentration also inhibited the binding of 125I-BSM and 125I-MSA III-2. For 125I-insulin binding, however, unlabeled MSA III-2 and MSA II were more effective than unlabeled insulin in displacing 125I-insulin from its binding sites. The binding sites for IGF-1 and IGF-II evidently are distinct in T-47D cells; insulin cross-reacts weakly with IGF-I and IGF-II binding sites. BSM (IGF-I) and MSA (IGF-II) (1 .mu.g/ml) produced a 1.5-fold increase in cell proliferation of T-47D cells grown on plastic substratum. The mitogenic effect of IGF on T-47D was more apparent when cells were grown on collagen gel. At 500 ng/ml, MSA, III-2, BSM and insulin stimulated cell growth 4-, 2.5- and 1.5-fold, respectively. IGF may be involved in the growth regulation of human breast cancer cells.

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