Estrogen and insulin modulation of intracellular insulin-like growth factor binding proteins in human breast cancer cells: possible involvement in lysosomal hydrolases oversecretion

Biochem Biophys Res Commun. 1993 Apr 15;192(1):295-301. doi: 10.1006/bbrc.1993.1413.

Abstract

Differences in insulin-like growth factor binding proteins (IGFBPs) expressed within estrogen receptor positive (ER+, MCF-7/6) and negative (ER-, MDA-MB-231) human breast cancer cells cultured in chemically defined medium were observed. In the absence of insulin, 17 beta-estradiol affects this expression in ER+ cells by significantly reducing 34 and 28 kDa species. In ER+ cells, insulin appears to minimize the estrogen induced reduction of these 34 and 28 kDa IGFBPs and stimulates a 24 kDa type. We suggest that through its association with a given IGFBP, insulin-like growth factor-II (IGF-II) directs lysosomal enzymes to secretion by its binding to the mannose-6-phosphate/IGF-II receptors present in the Golgi apparatus. Alternatively, the association of IGF-II with another IGFBP would inhibit this binding and lead to its autocrine or intracrine mitogenic action via the IGF-I receptor.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Breast Neoplasms / metabolism*
  • Carrier Proteins / metabolism*
  • Estrogens / physiology*
  • Humans
  • Hydrolases / metabolism*
  • Insulin / physiology*
  • Insulin-Like Growth Factor Binding Proteins
  • Lysosomes / enzymology*
  • Receptors, Estrogen / metabolism
  • Somatomedins / metabolism
  • Tumor Cells, Cultured

Substances

  • Carrier Proteins
  • Estrogens
  • Insulin
  • Insulin-Like Growth Factor Binding Proteins
  • Receptors, Estrogen
  • Somatomedins
  • Hydrolases