Effects of insulin-like growth factors (IGFs) and IGF receptor antibodies on the proliferation of human breast cancer cells

D. D. De Leon, D. M. Wilson, M. Powers, Ronald (Ron) Rosenfeld

Research output: Contribution to journalArticle

74 Citations (Scopus)

Abstract

It has been shown previously that MCF-7 cells proliferate in response to nanomolar concentrations of IGF-I and IGF-II. It has also been reported that the actions of both peptides are mediated through the IGF-I receptor. To further characterize these observations, we used MCF-7 and Hs578T cell lines in the serum-free/phenol red-free system developed by Ogasawara and Sibarsku, 1988. Cell proliferation was studied in the presence of insulin, IGF-I and-II and a series of growth factor receptor antibodies. No effect was observed on Hs578T cell proliferation with any of the growth factors. However, MCF-7 cells were stimulated 4-5 fold with IGF-I and insulin, while IGF-II was only slightly less potent. αIR3, a monoclonal antibody directed against the IGF-I receptor, was stimulatory when added alone. However, αIR3 blocked approximately 50% of the IGF-I response, only 5% of the insulin response, and did not block the IGF-II effect on cell proliferation. These data suggest that αIR3 and IGF-I are acting as agonists through the IGF-I receptor, but that insulin and IGF-II are acting through other receptors. Two different IGF-II/M-6-P receptor antibodies and an insulin receptor antibody failed to significantly block IGF-II actions. All three antibodies were stimulatory when added alone. βgal inhibited 27% of the IGF-II response and had no effect when added alone. Since βgal decreases the binding affinity of the IGF-II/M-6-P receptor for IGF-II and does not bind to the IGF-I or insulin receptor, these data suggest the possibility that IGF-II mitogenic action is mediated through the IGF-II/M-6-P receptor. In summary, these data indicate that nanomolar concentration of insulin, IGF-I and IGF-II are potent mitogens in MCF-7 cells and can potencially stimulate cell proliferation through all three receptors.

Original languageEnglish (US)
Pages (from-to)327-336
Number of pages10
JournalGrowth Factors
Volume6
Issue number4
DOIs
StatePublished - 1992
Externally publishedYes

Fingerprint

Somatomedin Receptors
Insulin-Like Growth Factor II
Somatomedins
Cells
Breast Neoplasms
Antibodies
Insulin-Like Growth Factor I
IGF Type 1 Receptor
Cell proliferation
MCF-7 Cells
Insulin
Cell Proliferation
Insulin Receptor
Phenolsulfonphthalein
IGF Type 2 Receptor
Insulin Antibodies
Growth Factor Receptors
Mitogens
Intercellular Signaling Peptides and Proteins
Monoclonal Antibodies

Keywords

  • Breast cancer
  • Insulin-like growth factors
  • MCF-7

ASJC Scopus subject areas

  • Clinical Biochemistry
  • Endocrinology
  • Cell Biology

Cite this

Effects of insulin-like growth factors (IGFs) and IGF receptor antibodies on the proliferation of human breast cancer cells. / De Leon, D. D.; Wilson, D. M.; Powers, M.; Rosenfeld, Ronald (Ron).

In: Growth Factors, Vol. 6, No. 4, 1992, p. 327-336.

Research output: Contribution to journalArticle

De Leon, D. D. ; Wilson, D. M. ; Powers, M. ; Rosenfeld, Ronald (Ron). / Effects of insulin-like growth factors (IGFs) and IGF receptor antibodies on the proliferation of human breast cancer cells. In: Growth Factors. 1992 ; Vol. 6, No. 4. pp. 327-336.
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