Regulation of breast cancer growth by insulin-like growth factors

J Steroid Biochem Mol Biol. 1990 Dec 20;37(6):805-9. doi: 10.1016/0960-0760(90)90423-i.


The IGFs may be important autocrine, paracrine or endocrine growth factors for human breast cancer. IGF-I and II stimulate growth of cultured human breast cancer cells. IGF-I is slightly more potent, paralleling its higher affinity for the IGF-I receptor. Antibody blockade of the IGF-I receptor inhibits growth stimulation induced by both IGFs, suggesting that this receptor mediates the growth effects of both peptides. However, IGF-I receptor blockade does not inhibit estrogen (E2)-induced growth suggesting that secreted IGFs are not the major mediators of E2 action. Several breast cancer cell lines express IGF-II mRNA by both Northern analysis and RNase protection assay. IGF-II activity is found in conditioned medium by radioimmuno and radioreceptor assay, after removal of somatomedin binding proteins (BP) which are secreted in abundance. IGF-I is undetectable. BPs of congruent to 25 and 40 K predominate in ER-negative cell lines while BPs of 36 K predominate in ER-positive cells. Blockade of the IGF-I receptor inhibits anchorage-independent and monolayer growth in serum of a panel of breast cancer cell lines. Growth of one line (MDA-231) was also inhibited in vivo by receptor antibody treatment of nude mice. The antibody had no effect on growth of MCF-7 tumors. These data suggest that IGFs are important regulators of breast cancer cell proliferation and that antagonism of this pathway may offer a new treatment strategy.

Publication types

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

MeSH terms

  • Antineoplastic Agents / pharmacology*
  • Breast Neoplasms / drug therapy*
  • Estrogens / pharmacology
  • Humans
  • Insulin-Like Growth Factor I / pharmacology*
  • Insulin-Like Growth Factor II / pharmacology*
  • Receptors, Cell Surface / metabolism
  • Receptors, Somatomedin
  • Tumor Cells, Cultured


  • Antineoplastic Agents
  • Estrogens
  • Receptors, Cell Surface
  • Receptors, Somatomedin
  • Insulin-Like Growth Factor I
  • Insulin-Like Growth Factor II