Insulin-like growth factors (IGFs) and
insulin are known to be mitogenic to a variety of cell types, although a growth-regulatory role of IGFs on human
breast cancer cells has not yet been fully investigated. In the present study, we examined the receptor binding and the effect on growth of IGFs and
insulin 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 has been 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. These observations suggest that the binding sites for
IGF-I and
IGF-II are distinct in T-47D cells and that
insulin cross-reacts weakly with
IGF-I and
IGF-II binding sites. BSM (
IGF-I) and MSA (
IGF-II) (1 microgram/ml) produced a 1.5-fold increase in cell proliferation of T-47D cells grown on
plastic substratum. The mitogenic effect of IGFs 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. Our results suggest that the IGFs may be involved in the growth regulation of human
breast cancer cells.