Reversal of cathepsin D routing modulation in MCF-7 breast cancer cells expressing antisense insulin-like growth factor II (IGF-II)

Daisy D. De León, Nadia Issa, Stephanie Nainani, Yayesh Asmerom

Research output: Contribution to journalArticle

15 Scopus citations

Abstract

We previously demonstrated that expression of IGF-II modulates the routing of cathepsin D in MCF-7 cells. In our present study, we transfected antisense IGF-II into IGF-II secreting MCF-7 cells to test the hypothesis that blocking IGF-II may reduce the secretion of cathepsin D in breast cancer cells. The concentration of IGF-II in media conditioned by the antisense clone was reduced to almost undetectable levels. Likewise, Northern blotting analysis revealed that IGF-II mRNA was nearly undetectable in the antisense transfected cells. Metabolic labeling experiments performed with 10 mM mannose 6-phosphate present in the medium to block reuptake of lysosomal enzymes demonstrated that cathepsin D secretion was dramatically reduced. Similarly, a significant reduction in cathepsin D was observed when conditioned media and cell extracts were examined by Western blotting after a 48 h incubation. No changes in cathepsin D mRNA in antisense cells were detected by Northern blot analysis. We conclude that endogenous IGF-II may modulate the routing of cathepsin D by interfering with receptor trafficking in MCF-7 cells, and that this modulation is reversible. Abnormally high levels of IGF-II may alter this homeostasis, conferring on breast cancer cells an advantageous mechanism that promotes rapid growth, and may faciliate metastasis.

Original languageEnglish (US)
Pages (from-to)142-147
Number of pages6
JournalHormone and Metabolic Research
Volume31
Issue number2-3
StatePublished - Apr 20 1999

Keywords

  • Breast cancer
  • Cathepsin D
  • IGF-II/Mannose 6- phosphate receptor
  • Insulin-like growth factor II (IGF-II)
  • MCF-7 cells

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Biochemistry
  • Endocrinology
  • Clinical Biochemistry
  • Biochemistry, medical

Fingerprint Dive into the research topics of 'Reversal of cathepsin D routing modulation in MCF-7 breast cancer cells expressing antisense insulin-like growth factor II (IGF-II)'. Together they form a unique fingerprint.

  • Cite this