Insulin-like growth factor-II (IGF-II): a potential autocrine/paracrine growth factor for human breast cancer acting via the IGF-I receptor

Mol Endocrinol. 1989 Nov;3(11):1701-9. doi: 10.1210/mend-3-11-1701.


Insulin-like growth factor-II (IGF-II) is a potent mitogen for several types of cultured cells and tissues. We have studied the interaction of IGF-II with a panel of cultured human breast cancer cell lines, examining the possibility that these cells synthesize and secrete IGF-II activity which could have autocrine/paracrine functions. Synthetic IGF-II was mitogenic in five of seven cell lines tested, including the estrogen receptor-positive lines MCF-7L, ZR75-1, and T47D and the estrogen receptor (ER)-negative lines Hs578T and MDA-231. IGF-II was slightly less potent than IGF-I in stimulating DNA synthesis in MCF-71 cells, an effect that paralleled its ability to compete for [125I]IGF-I binding in these cells. Affinity labeling studies revealed that IGF-II could also compete for binding to the 130,000 mol wt alpha-subunit of the IGF-I receptor. A monoclonal antibody to the IGF-I receptor inhibited the mitogenic effects of IGF-II in MCF-7L and MDA-231 cells, suggesting that this receptor mediates the growth effects of IGF-II in these breast cancer cells. Using a RIA and a RRA, IGF-II-like activity was detected in conditioned medium extracts processed to remove IGF-binding proteins from several breast cancer cell lines, with the highest levels found in conditioned medium from MCF-7L and T47D cell lines. IGF-II mRNA transcripts in MCF-7L and T47D cells were identified by Northern blot analysis and were confirmed by RNase protection assay. IGF-II mRNA was increased by estrogen in MCF-7L cells.(ABSTRACT TRUNCATED AT 250 WORDS)

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Binding, Competitive
  • Breast Neoplasms / pathology*
  • Cell Division / drug effects
  • DNA Replication / drug effects
  • DNA, Neoplasm / biosynthesis
  • Estrogens
  • Gene Expression Regulation, Neoplastic
  • Hormones / pharmacology
  • Insulin-Like Growth Factor I / metabolism
  • Insulin-Like Growth Factor II / metabolism
  • Insulin-Like Growth Factor II / pharmacology*
  • Neoplasms, Hormone-Dependent / pathology
  • RNA, Messenger / biosynthesis
  • RNA, Neoplasm / biosynthesis
  • Receptors, Cell Surface / drug effects*
  • Receptors, Cell Surface / metabolism
  • Receptors, Somatomedin
  • Somatomedins / pharmacology*
  • Tumor Cells, Cultured / drug effects
  • Tumor Cells, Cultured / metabolism
  • Tumor Cells, Cultured / pathology


  • DNA, Neoplasm
  • Estrogens
  • Hormones
  • RNA, Messenger
  • RNA, Neoplasm
  • Receptors, Cell Surface
  • Receptors, Somatomedin
  • Somatomedins
  • Insulin-Like Growth Factor I
  • Insulin-Like Growth Factor II