Modulation of cathepsin D routing by IGF-II involves IGF-II binding to IGF-II/M6P receptor in MCF-7 breast cancer cells

Growth Factors. 2004 Sep;22(3):169-77. doi: 10.1080/08977190410001725531.

Abstract

The IGF-II/M6P receptor targets cathepsin D to the lysosomes and it also binds IGF-II. Although the binding sites for IGF-II and cathepsin D are distinct, reciprocal interactions between the ligands have been observed. We have demonstrated that proIGF-II expression modulates routing of cathepsin D. To test the hypothesis that IGF-II modulation of cathepsin D routing in MCF-7 cells involves IGF-II binding to the IGF-II/M6P receptor, we expressed a mutant form of IGF-II (Arg54 Arg55) that does not bind the IGF-II/M6P receptor and evaluated its effects on cathepsin D secretion. Northern blotting, Western and radioimmunoassay analyses confirmed that these cells express high levels of (Arg54 Arg55) IGF-II mRNA and secretes high levels of IGF-II without modulating the secretion of cathepsin D. These data provide direct evidence that the IGF-II modulation of cathepsin D routing is IGF-II/M6P receptor mediated.

Publication types

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

MeSH terms

  • Animals
  • Arginine / chemistry
  • Blotting, Northern
  • Blotting, Western
  • Breast Neoplasms / metabolism
  • Cathepsin D / chemistry
  • Cathepsin D / metabolism*
  • Cell Line
  • Cell Line, Tumor
  • Culture Media, Conditioned / pharmacology
  • DNA, Complementary / metabolism
  • Dose-Response Relationship, Drug
  • Genetic Vectors
  • Humans
  • Immunoblotting
  • Immunoprecipitation
  • Insulin-Like Growth Factor II / metabolism*
  • Lysosomes / metabolism
  • Mice
  • Microsomes, Liver / metabolism
  • RNA, Messenger / metabolism
  • Radioimmunoassay
  • Time Factors
  • Transfection

Substances

  • Culture Media, Conditioned
  • DNA, Complementary
  • RNA, Messenger
  • Insulin-Like Growth Factor II
  • Arginine
  • Cathepsin D